PMID- 19474207 TI - Differential modulation of NF-kappaB-mediated pro-inflammatory response in human intestinal epithelial cells by cheY homologues of Vibrio cholerae. AB - Vibrio cholerae, the etiological agent of cholera, colonizes the small intestine, produces an enterotoxin and causes acute inflammatory response at intestinal epithelial surface. Chemotaxis and motility greatly influence the infectivity of V. cholerae although the role of chemotaxis genes in V. cholerae pathogenesis is less well understood. Four cheY genes are present in three clusters in the complete genome sequence of V. cholerae. A less motile and less adherent mutant was generated by inactivation of cheY-3 (O395Y3N) or cheY-4 (O395Y4N) whereas alterations in motility or adherence were not observed for cheY-1 (O395Y1N) or cheY-2 (O395Y2N) insertional mutants. In contrast to O395Y1N and O395Y2N, O395Y3N and O395Y4N showed reduced cholera toxin production compared to wild-type in vitro. Infection of the human intestinal epithelial cell line Int407 with O395Y3N and O395Y4N caused reduced secretion of interleukin (IL)-1a, IL-6, tumor necrosis factor (TNF-a) and monocyte chemotactic protein-1 (MCP-1) compared to wild-type and was associated with delayed activation of nuclear factor kappa B (NF-kappaB) p65 and its co-activator cAMP response element binding protein (CREB). Further, the absence of nuclear translocation of NF-kappaB p50 subunit upon infection with O395Y3N or O395Y4N and its reversal upon complementation indicates the involvement of cheY-3 and cheY-4 in V. cholerae-induced pro-inflammatory response in the INT407 cell line. PMID- 19474208 TI - Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen. AB - Based on the common characteristic of severe acute respiratory syndrome (SARS) and highly pathogenic avian influenza and the mechanism of inflammation and fibrosis, it is speculated that there should exist a fundamental pathological rule that severe acute lung injury (ALI)-induced rapid pulmonary fibrosis is caused by various etiological factors, such as SARS coronavirus, H5N1-virus, or other unknown factors, and also by lipopolysaccharide (LPS), the most common etiological factor. The investigation employed intratracheally, and intraperitoneally and intratracheally applied LPS three-hit regimen, compared with bleomycin-induced chronic pulmonary fibrosis. Inflammatory damage and fibrosis were evaluated, and the molecular mechanism was analyzed according to Th1/Th2 balance, Sma- and MAD-related proteins (Smads) and signal transducer and activator of transcriptions (STATs) expression. The results suggested that rapid pulmonary fibrosis could be induced by ALI via LPS three-hits. The period from 3 7 days in the LPS group was the first rapid pulmonary fibrosis stage, whereas the second fast fibrosis stage occurred on days 14-21. Th2 cell polarization, Smad4 and Smad7 should be the crucial molecular mechanism of ALI-induced rapid fibrosis. The investigation was not only performed to establish a new rapid pulmonary fibrosis model, but also to provide the elicitation for mechanism of ALI changed into the rapid pulmonary fibrosis. PMID- 19474206 TI - Orthotopic and heterotopic ovarian tissue transplantation. AB - BACKGROUND: Transplantation of ovarian tissue is, at present, the only clinical option available to restore fertility using cryopreserved ovarian tissue. More than 30 transplantations of cryopreserved tissue have been reported, and six babies have been born, worldwide, following this procedure. Despite these encouraging results, it is essential to optimize the procedure by improving the follicular survival, confirming safety and developing alternatives. Here, we review the different factors affecting follicular survival and growth after grafting. METHODS: Relevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting. RESULTS: Clinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established. CONCLUSION: Additional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future. PMID- 19474209 TI - Activation of Toll-like receptors 2 and 4 in Aspergillus fumigatus keratitis. AB - Toll-like receptor (TLR) 2 and TLR4 are major receptors of Aspergillus fumigatus. Aspergillus fumigatus signaling in cornea induces the production of many pro inflammatory molecules. In this study, we have shown that exposure of telomerase immortalized human corneal epithelial cells (HCECs) to A. fumigatus antigens resulted in up-regulation of TLR2 and TLR4, and release of IL-1beta and IL-10 in HCECs, effects that could be inhibited by treatment with TLR2, and TLR4 antibodies. In addition, the A. fumigatus antigens-induced production of IL-1beta and IL-10 in supernatants of corneal epithelial cells was also attenuated by NF kappaB inhibitor. Aspergillus fumigatus keratitis developed in Wistar rats, as evidenced by high SLE scores, influx of polymorphonuclear leukocytes (PMNs), activation of TLR2 and TLR4, and production of IL-1beta and IL-10 over controls. These findings indicate that the cornea has functional TLR2 and TLR4, and activation of TLR2 and TLR4 through NF-kappaB may contribute to pathogenesis of keratomycosis. PMID- 19474210 TI - Activation of peroxisome proliferator-activated receptor-gamma potentiates pro inflammatory cytokine production, and adrenal and somatotropic changes of weaned pigs after Escherichia coli lipopolysaccharide challenge. AB - Our previous study demonstrated mRNA and protein expression of peroxisome proliferator-activated receptor-g (PPAR-g) in the immune system of weaned pigs. In this report, to test the hypothesis that activation of PPAR-g in immune system modulates inflammatory response, and adrenal and somatotropic responses associated with immune challenge, we administered intraperitoneally PPAR-g agonist and/or antagonist in weaned pigs subjected to Escherichia coli lipopolysaccharide (LPS) challenge. Unexpectedly, we found that a single injection of the PPAR-g agonist rosiglitazone (given at 3 mg/kg body weight 30 min before LPS injection) failed to block pro-inflammatory cytokine production induced by LPS injection. Rather, plasma levels of tumor necrosis factor-a (TNF a) and interleukin-6 (IL-6), mRNA abundance of TNF-a in thymus, spleen, mesenteric lymph node and peripheral white blood cells, mRNA abundance of IL-6 in thymus, protein levels of TNF-a in spleen and mesenteric lymph node, and protein levels of IL-6 in spleen and mesenteric lymph node, were elevated beyond the levels in control pigs injected with LPS. Furthermore, rosiglitazone potentiated the increase of plasma cortisol and prostaglandin E(2) concentrations, and the decrease of plasma insulin-like growth factor-1 concentration induced by LPS injection. Co-administration of the PPAR-g antagonist bisphenol A diglycidyl ether (given 30 mg/kg body weight) 30 min prior to treatment with rosiglitazone antagonized the effect of the PPAR-g agonist, indicating a PPAR-g-dependent effect. Our data indicate that ligand-induced activation of PPAR-g does not ameliorate but enhances pro-inflammatory cytokine production, and further potentiates the adrenal and somatotropic changes in weaned pigs subjected to E. coli LPS challenge, which suggests that PPAR-g activation may not be useful, but potentially harmful, in the treatment of immune challenge in livestock. Our results raise doubts about the prevalently accepted anti-inflammatory role for PPAR-g activation. PMID- 19474211 TI - Review: Immunity mechanisms in crustaceans. AB - Crustacean aquaculture represents a major industry in tropical developing countries. As a result of high culture densities and increasing extension of aquaculture farms, the presence of diseases has also increased, inducing economic losses. Invertebrates, which lack adaptive immune systems, have developed defense systems that respond against antigens on the surface of potential pathogens. The defense mechanisms of crustaceans depend completely on the innate immune system that is activated when pathogen-associated molecular patterns are recognized by soluble or by cell surface host proteins, such as lectins, antimicrobial, clotting, and pattern recognition proteins, which, in turn, activate cellular or humoral effector mechanisms to destroy invading pathogens. This work is aimed at presenting the main characteristics of the crustacean proteins that participate in immune defense by specific recognition of carbohydrate containing molecules, i.e. glycans, glycolipids, glycoproteins, peptidoglycans, or lipopolysaccharides from Gram-negative and Gram-positive bacteria, viruses, or fungi. We review some basic aspects of crustacean effector defense processes, like agglutination, encapsulation, phagocytosis, clottable proteins, and bactericidal activity, induced by these carbohydrate-driven recognition patterns. PMID- 19474212 TI - The RNA hydrolysis and the cytokinin binding activities of PR-10 proteins are differently performed by two isoforms of the Pru p 1 peach major allergen and are possibly functionally related. AB - PR-10 proteins are a family of pathogenesis-related (PR) allergenic proteins playing multifunctional roles. The peach (Prunus persica) major allergen, Pru p 1.01, and its isoform, Pru p 1.06D, were found highly expressed in the fruit skin at the pit hardening stage, when fruits transiently lose their susceptibility to the fungal pathogen Monilinia spp. To investigate the possible role of the two Pru p 1 isoforms in plant defense, the recombinant proteins were expressed in Escherichia coli and purified. Light scattering experiments and circular dichroism spectroscopy showed that both proteins are monomers in solution with secondary structures typical of PR-10 proteins. Even though the proteins do not display direct antimicrobial activity, they both act as RNases, a function possibly related to defense. The RNase activity is different for the two proteins, and only that of Pru p 1.01 is affected in the presence of the cytokinin zeatin, suggesting a physiological correlation between Pru p 1.01 ligand binding and enzymatic activity. The binding of zeatin to Pru p 1.01 was evaluated using isothermal titration calorimetry, which provided information on the stoichiometry and on the thermodynamic parameters of the interaction. The structural architecture of Pru p 1.01 and Pru p 1.06D was obtained by homology modeling, and the differences in the binding pockets, possibly accounting for the observed difference in binding activity, were evaluated. PMID- 19474213 TI - Fine-tuning of the cytoplasmic Ca2+ concentration is essential for pollen tube growth. AB - Pollen tube growth is crucial for the delivery of sperm cells to the ovule during flowering plant reproduction. Previous in vitro imaging of Lilium longiflorum and Nicotiana tabacum has shown that growing pollen tubes exhibit a tip-focused Ca(2+) concentration ([Ca(2+)]) gradient and regular oscillations of the cytosolic [Ca(2+)] ([Ca(2+)](cyt)) in the tip region. Whether this [Ca(2+)] gradient and/or [Ca(2+)](cyt) oscillations are present as the tube grows through the stigma (in vivo condition), however, is still not clear. We monitored [Ca(2+)](cyt) dynamics in pollen tubes under various conditions using Arabidopsis (Arabidopsis thaliana) and N. tabacum expressing yellow cameleon 3.60, a fluorescent calcium indicator with a large dynamic range. The tip-focused [Ca(2+)](cyt) gradient was always observed in growing pollen tubes. Regular oscillations of the [Ca(2+)](cyt), however, were rarely identified in Arabidopsis or N. tabacum pollen tubes grown under the in vivo condition or in those placed in germination medium just after they had grown through a style (semi-in vivo condition). On the other hand, regular oscillations were observed in vitro in both growing and nongrowing pollen tubes, although the oscillation amplitude was 5-fold greater in the nongrowing pollen tubes compared with growing pollen tubes. These results suggested that a submicromolar [Ca(2+)](cyt) in the tip region is essential for pollen tube growth, whereas a regular [Ca(2+)] oscillation is not. Next, we monitored [Ca(2+)] dynamics in the endoplasmic reticulum ([Ca(2+)](ER)) in relation to Arabidopsis pollen tube growth using yellow cameleon 4.60, which has a lower affinity for Ca(2+) compared with yellow cameleon 3.60. The [Ca(2+)](ER) in pollen tubes grown under the semi-in vivo condition was between 100 and 500 microm. In addition, cyclopiazonic acid, an inhibitor of ER-type Ca(2+)-ATPases, inhibited growth and decreased the [Ca(2+)](ER). Our observations suggest that the ER serves as one of the Ca(2+) stores in the pollen tube and cyclopiazonic acid-sensitive Ca(2+)-ATPases in the ER are required for pollen tube growth. PMID- 19474215 TI - Simultaneous targeting of multiple opioid receptors: a strategy to improve side effect profile. AB - Opioid receptors are currently classified as mu (mu: mOP), delta (delta: dOP), kappa (kappa: kOP) with a fourth related non-classical opioid receptor for nociceptin/orphainin FQ, NOP. Morphine is the current gold standard analgesic acting at MOP receptors but produces a range of variably troublesome side effects, in particular tolerance. There is now good laboratory evidence to suggest that blocking DOP while activating MOP produces analgesia (or antinociception) without the development of tolerance. Simultaneous targeting of MOP and DOP can be accomplished by: (i) co-administering two selective drugs, (ii) administering one non-selective drug, or (iii) designing a single drug that specifically targets both receptors; a bivalent ligand. Bivalent ligands generally contain two active centres or pharmacophores that are variably separated by a chemical spacer and there are several interesting examples in the literature. For example linking the MOP agonist oxymorphone to the DOP antagonist naltrindole produces a MOP/DOP bivalent ligand that should produce analgesia with reduced tolerance. The type of response/selectivity produced depends on the pharmacophore combination (e.g. oxymorphone and naltrindole as above) and the space between them. Production and evaluation of bivalent ligands is an emerging field in drug design and for anaesthesia, analgesics that are designed not to be highly selective morphine-like (MOP) ligands represents a new avenue for the production of useful drugs for chronic (and in particular cancer) pain. PMID- 19474214 TI - Refining the definition of plant mitochondrial presequences through analysis of sorting signals, N-terminal modifications, and cleavage motifs. AB - Mitochondrial protein import is a complex multistep process from synthesis of proteins in the cytosol, recognition by receptors on the organelle surface, to translocation across one or both mitochondrial membranes and assembly after removal of the targeting signal, referred to as a presequence. In plants, import has to further discriminate between mitochondria and chloroplasts. In this study, we determined the precise cleavage sites in the presequences for Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) mitochondrial proteins using mass spectrometry by comparing the precursor sequences with experimental evidence of the amino-terminal peptide from mature proteins. We validated this method by assessments of false-positive rates and comparisons with previous available data using Edman degradation. In total, the cleavable presequences of 62 proteins from Arabidopsis and 52 proteins from rice mitochondria were determined. None of these proteins contained amino-terminal acetylation, in contrast to recent findings for chloroplast stromal proteins. Furthermore, the classical matrix glutamate dehydrogenase was detected with intact and amino-terminal acetylated sequences, indicating that it is imported into mitochondria without a cleavable targeting signal. Arabidopsis and rice mitochondrial presequences had similar isoelectric points, hydrophobicity, and the predicted ability to form an amphiphilic alpha helix at the amino-terminal region of the presequence, but variations in length, amino acid composition, and cleavage motifs for mitochondrial processing peptidase were observed. A combination of lower hydrophobicity and start point of the amino-terminal alpha-helix in mitochondrial presequences in both Arabidopsis and rice distinguished them (98%) from Arabidopsis chloroplast stroma transit peptides. Both Arabidopsis and rice mitochondrial cleavage sites could be grouped into three classes, with conserved -3R (class II) and -2R (class I) or without any conserved (class III) arginines. Class II was dominant in both Arabidopsis and rice (55%-58%), but in rice sequences there was much less frequently a phenylalanine (F) in the -1 position of the cleavage site than in Arabidopsis sequences. Our data also suggest a novel cleavage motif of (F/Y) downward arrow(S/A) in plant class III sequences. PMID- 19474216 TI - Immunomodulation in the critically ill. AB - Immunotherapy in the critically ill is an appealing notion because of the apparent abnormal immune and inflammatory responses seen in so many patients. The administration of a medication that could alter immune responses and decrease mortality in patients with sepsis could represent a 'magic bullet'. Various approaches have been tried over the last 20 yr: steroids; anti-endotoxin or anti cytokine antibodies; cytokine receptor antagonists; and other agents with immune modulating side-effects. However, in some respects, research along these lines has been unsuccessful or disappointing at best. The current state of knowledge is summarized with particular reference to sepsis and the acute respiratory distress syndrome. PMID- 19474217 TI - Both NR2A and NR2B subunits of the NMDA receptor are critical for long-term potentiation and long-term depression in the lateral amygdala of horizontal slices of adult mice. AB - The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs coexist in synapses of LA projection neurons. We assessed the contribution of the two NMDAR subtypes to LA-LTP and LA-LTD in adult mouse brain slices by different induction protocols and by different inputs to LA neurons in the presence of different NMDAR subunit antagonists. In general, our results indicate that both NR2A and NR2B subunits are required for the formation of LA-LTP and LA-LTD. The abolishment or reduction of plasticity changes by these compounds could be due to the reduction in calcium influx via NMDARs. We also show, to our knowledge for the first time, that paired-pulse (40-msec interstimulus interval), low-frequency stimulation of external capsule fibers causes stable LTD. Rather than resulting from exclusive roles of the NMDAR subtypes, the synaptic plasticity response in the amygdala appears to be directed by the pattern of synaptic activation and the used inputs, which recruit the major NMDAR subtypes to variable extents. PMID- 19474218 TI - Protein profiles in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonate. AB - Perfluorooctane sulfonate (PFOS) is widely distributed and persistent in the environment and in wildlife, and it has the potential for developmental toxicity. However, the molecular mechanisms that lead to these toxic effects are not well known. In the present study, proteomic analysis has been performed to investigate the proteins that are differentially expressed in zebrafish embryos exposed to 0.5 mg/l PFOS until 192 h postfertilization. Two-dimensional electrophoresis coupled with mass spectrometry was employed to detect and identify the protein profiles. The analysis revealed that 69 proteins showed altered expression in the treatment group compared to the control group with either increase or decrease in expression levels (more than twofold difference). Of the 69 spots corresponding to the proteins with altered expression, 38 were selected and subjected to matrix assisted laser desorption/ionization tandem time-of-flight mass spectrometry (TOF/TOF) analysis; 18 proteins were identified in this analysis. These proteins can be categorized into diverse functional classes such as detoxification, energy metabolism, lipid transport/steroid metabolic process, cell structure, signal transduction, and apoptosis. Overall, proteomic analysis using zebrafish embryos serves as an in vivo model in environmental risk assessment and provides insight into the molecular events in PFOS-induced developmental toxicity. PMID- 19474219 TI - Mechanism of thiol-supported arsenate reduction mediated by phosphorolytic arsenolytic enzymes: I. The role of arsenolysis. AB - Several mammalian enzymes catalyzing the phosphorolytic-arsenolytic cleavage of their substrates (thus yielding arsenylated metabolites) have been shown to facilitate reduction of arsenate (AsV) to the more toxic arsenite (AsIII) in presence of their substrate and a thiol. These include purine nucleoside phosphorylase (PNP), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycogen phosphorylase-a (GPa). In this work, we tested further enzymes, the bacterial phosphotransacetylases (PTAs) and PNP, for AsV reduction. The PTAs, which arsenolytically cleave acetyl-CoA producing acetyl-arsenate, were compared with GAPDH, which can also form acetyl-arsenate by arsenolysis of its nonphysiological substrate, acetyl-phosphate. As these enzymes also mediated AsV reduction, we can assert that facilitation of thiol-dependent AsV reduction may be a general property of enzymes that catalyze phosphorolytic-arsenolytic reactions. Because with all such enzymes arsenolysis is obligatory for AsV reduction, we analyzed the relationship between these two processes in presence of various thiol compounds, using PNP. Although no thiol influenced the rate of PNP-catalyzed arsenolysis, all enhanced the PNP-mediated AsV reduction, albeit differentially. Furthermore, the relative capacity of thiols to support AsV reduction mediated by PNP, GPa, PTA, and GAPDH apparently depended on the type of arsenylated metabolites (i.e., arsenate ester or anhydride) produced by these enzymes. Importantly, AsV reduction by both acetyl-arsenate-producing enzymes (i.e., PTA and GAPDH) exhibited striking similarities in responsiveness to various thiols, thus highlighting the role of arsenylated metabolite formation. This observation, together with the finding that PNP-mediated AsV reduction lags behind the PNP-catalyzed arsenolysis lead to the hypothesis that arsenolytic enzymes promote reduction of AsV by forming arsenylated metabolites which are more reducible to AsIII by thiols than inorganic AsV. This hypothesis is evaluated in the adjoining paper. PMID- 19474221 TI - From pull to push: understanding nurses' information needs. AB - Electronic access to research information for health professionals is a key component in developing evidence-based healthcare. As nurses take on extended roles and work more autonomously, it is assumed that they will take increasing advantage of these technologies. However, little is known about the decisions that nurses make and the information needs that arise within the context of those decisions. This article presents an analysis of 410 nurse-patient consultations and interviews with 76 primary care nurses, and explores nurses' information needs and their use of electronic information tools. The findings suggest that, if we wish to encourage nurses to use research information in clinical practice, we need to move from 'pull' to 'push' technology. PMID- 19474220 TI - Introducing the "TCDD-inducible AhR-Nrf2 gene battery". AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces genes via the transcription factor aryl hydrocarbon receptor (AhR), including Cyp1a1, NAD(P)H:quinone oxidoreductase 1 (Nqo1), UDP-glucuronosyltransferase 1a6 (Ugt1a6), and glutathione S-transferase a1 (Gsta1). These genes are referred to as the "AhR gene battery." However, Nqo1 is also considered a prototypical target gene of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). In mice, TCDD induction of Nrf2 and Nrf2 target, Nqo1, is dependent on AhR, and thus TCDD induction of drug-processing genes may be routed through an AhR-Nrf2 sequence. There has been speculation that Nrf2 may be involved in the TCDD induction of drug-processing genes; however, the data are not definitive. Therefore, to address whether TCDD induction of Nqo1, Ugts, and Gsts is dependent on Nrf2, we conducted the definitive experiment by administering TCDD (50 mug/kg, ip) to Nrf2 null and wild-type (WT) mice and collecting livers 24 h later to quantify the mRNA of drug-processing genes. TCDD induction of Cyp1a1 and Ugt1a1 was similar in WT and Nrf2-null mice, whereas TCDD induction of Ugt1a5 and 1a9 was blunted in Nrf2-null mice. TCDD induced Nqo1, Ugt1a6, 2b34, 2b35, 2b36, UDP-glucuronic acid synthesizing gene UDP-glucose dehydrogenase, and Gsta1, m1, m2, m3, m6, p2, t2, and microsomal Gst1 in WT mice but not in Nrf2-null mice. Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice. PMID- 19474222 TI - Does a post-take ward round proforma have a positive effect on completeness of documentation and efficiency of information management? AB - The post-take ward round (PTWR) involves the assessment of the latest intake of patients into the hospital. At a busy 400-bed city hospital it had been noted that PTWR notes had, in some cases, become overly brief and uninformative. Previous research had shown that proformas can improve the completeness of the records. So a new proforma was designed and introduced. Its impact on completeness of information was assessed by carrying out an audit of PTWR notes both with and without the proforma. The results showed statistically significant improvements in documentation when the proforma was used. They also showed an improvement in areas of efficiency of record management: for example, the proforma reduced the time taken to retrieve information from the notes, and most users said it saved them time recording in the notes and assimilating information and helped them to speed up patient transfers. PMID- 19474223 TI - System dynamics approach to immunization healthcare issues in developing countries: a case study of Uganda. AB - This article critically examines the challenges associated with demand for immunization, including the interplay of political, social, economic and technological forces that influence the level of immunization coverage. The article suggests a framework to capture the complex and dynamic nature of the immunization process and tests its effectiveness using a case study of Ugandan healthcare provision. Field study research methods and qualitative system dynamics, a feedback and control theory based modelling approach, are used to capture the complexity and dynamic nature of the immunization process, to enhance a deeper understanding of the immunization organizational environment. A model showing the dynamic influences associated with demand and provision of immunization services, with the aim of facilitating the decision making process as well as healthcare policy interventions, is presented. PMID- 19474224 TI - Reflections on the use of electronic health record data for clinical research. AB - The adoption of electronic health records (EHRs) offers the potential to improve the delivery, quality, and continuity of clinical care, but widespread use has not yet occurred. In this article, we describe our use of clinical (production) data that were derived from outpatient and inpatient visits at a university teaching hospital for clinical research, a use for which the data and their structure were not originally designed. Similar data exist at many outpatient and inpatient clinical facilities, and we believe that our insights are relevant to electronically captured medical data regardless of their origin. We describe the approaches taken to ensure compliance with the Health Insurance Portability and Accountability Act (HIPAA) and to leverage the vast stores of structured and unstructured data that are currently underused. We conclude by reflecting on what we would have done differently and by making recommendations to streamline the process. PMID- 19474225 TI - The role of home-based information and communications technology interventions in chronic disease management: a systematic literature review. AB - This article presents a systematic literature review done to evaluate the feasibility and benefits of home-based information and communications technology enabled interventions for chronic disease management, with emphasis on their impact on health outcomes and costs. Relevant articles were retrieved from PubMed and evaluated using quality worksheets with pre-identified inclusion and exclusion criteria. Of the 256 articles retrieved, 27 were found to concord with the study criteria. Evaluation of the identified articles was conducted irrespective of study design, type of home-based intervention or chronic disease involved. The review demonstrates that HBIs applied to chronic disease management improve functional and cognitive patient outcomes and reduce healthcare spending. However, further research is needed to assess benefit in terms of evidence-based outcome indicators (that can provide a basis for meta-analysis), to confirm sustainable cost benefits, and to systematically collect data on physician satisfaction with patient management. PMID- 19474226 TI - Patients' views of a multimedia resource featuring experiences of rheumatoid arthritis: pilot evaluation of www.healthtalkonline.org. AB - The Internet is used increasingly for health information and patient support. Online health information users gravitate to websites that feature patient experiences. However, experiential accounts may mislead if they are unrepresentative. The quality of experiential websites remains unexplored. Obtaining user feedback online can be problematic. This study explored views of www.dipex.org/arthritis, a website based on, and featuring, clips from interviews about experiences of rheumatoid arthritis (RA). Thirty-seven rheumatology outpatients viewed the site and completed a questionnaire. Overall the website appeared relevant and understandable and could be recommended. Comments highlighted the need to update the site regularly with experiences of new treatments; to ensure positive and negative experiences are balanced; and to ensure information is easy to find. The site has since been updated with new experiences and rewritten summaries that present a better balance of experiences. Changes were incorporated in an entire site redesign launched in autumn 2008 as www.healthtalkonline.org. PMID- 19474227 TI - Early crossbite correction: a three-dimensional evaluation. AB - A crossbite (CB) occurs in approximately 4-23 per cent of young children and may lead to mandibular and facial asymmetry. Therefore, early intervention is often necessary to create conditions for normal occlusal and facial development. The aim of this study was to assess facial asymmetry and palatal volume (pre- and post-treatment) in two groups of children, one with a unilateral CB and the other with no crossbite (NCB). Thirty children with CB (13 males, 17 females, mean age 4.9 +/- 0.98 years) and 28 children with NCB (17 males, 11 females, mean age 5.3 +/- 0.36 years) were included in the study. Those with a CB were treated with an intra-oral expansion appliance. The faces and dental casts of the children were scanned using a three-dimensional (3D) laser scanning device at baseline (T0) and after six months (T1) of treatment. Student's t-tests were used to assess differences between the two groups in facial symmetry and palatal volume over the 6 month period. The CB children had statistically significantly greater asymmetry of the face (P = 0.042), especially the lower third (P = 0.039), and a significantly smaller palatal volume (P = 0.045) than the NCB subjects at baseline. There were no statistically significant differences between the two groups at T1. Treatment of a CB in the primary dentition corrected the facial asymmetry, particularly the lower part of the face. The palatal volume of the CB children increased as a result of orthodontic intervention to similar levels exhibited by the NCB children. PMID- 19474228 TI - Measurement of discolouration of orthodontic elastomeric modules with a digital camera. AB - The objective of this study was to measure discolouration using a digital camera on various types of clear orthodontic elastic modules, immersion solutions, and time periods to determine whether the cause of discolouration of these modules was due to simple staining, chemical degradation, or both. Three types of clear orthodontic elastomeric modules were investigated [Plastic ligatures (AO); Power 'O's 012 (OC); dispense-A-tie (TP)]. The elastomeric modules were immersed in the stretched condition in distilled water (control group) and in 75 per cent ethanol for chemical degradation and 2 per cent methylene blue for simple staining. After 0, 1, 2, 3, 6, 9, 12, 15, 18, and 21 hours and 1, 2, 3, 4, and 5 days of immersion, digital images of the modules were taken and processed using commercial software. The differences in colour changes depending on the type of elastomeric modules, immersion solution, and immersion period were analysed using a three-way analysis of variance and Tukey's multiple comparison test. The colour changes in the ethanol and methylene blue solutions by immersion period were analysed with regression analysis. There were significant differences in discolouration depending on the type of elastomeric modules, immersion solution, and immersion period (P < 0.05). The range of colour changes (Delta E* ab) was 1.0-20.0 units for AO, 0.6-30.0 units for OC, and 1.1-18.8 units for TP, independent of immersion solution and time. Methylene blue resulted in the greatest colour change. Discolouration due to chemical degradation by the ethanol solution mainly occurred in the first few hours, reached a plateau with no further increase over time, and was greater than staining by methylene blue in that period. Discolouration due to staining by methylene blue, however, continued to increase over the whole immersion period. Therefore, discolouration of elastomeric modules was a result of chemical degradation as well as staining in the early stages but in the later stages was due only to simple staining. PMID- 19474229 TI - Salivary Streptococcus mutans levels in patients with conventional and self ligating brackets. AB - The objective of this study was to investigate the effect of bracket type (conventional and self-ligating) on the levels of Streptococcus mutans and total bacterial counts in whole saliva of orthodontic patients. Thirty-two male and female patients were selected using the following inclusion criteria: adolescents (mean age 13.6 years, range 11-17 years), fixed appliances in both arches, non smoker, and no reported oral habits. Demographic and oral hygiene characteristics were determined for each subject. The patients were subdivided into two groups with random allocation of bracket type (conventional or self-ligating). An initial saliva sample was obtained before the initiation of treatment (T1) and a second sample 2-3 months following appliance bonding (T2). Salivary S. mutans and total bacteria were enumerated and analysed after growth in culture. The demographic and clinical characteristics of the samples were analysed with a t- or chi-square test, where applicable, to assess the random allocation of bracket group to participants. The results of S. mutans and total facultative bacterial counts were log transformed and statistically analysed with analysis of covariance with bracket (conventional versus self-ligating) as the categorical variable and initial total bacterial counts or initial S. mutans levels serving as the covariate. No difference was found in the demographics and oral hygiene indices between the two groups, verifying the random assignment of brackets to the population sample. The levels of S. mutans in whole saliva of orthodontically treated patients do not seem to be significantly different between conventional and self-ligating brackets. The pre-treatment levels of S. mutans are significant predictors of the levels of S. mutans after placement of orthodontic appliances, while this was not the case for total bacterial counts. PMID- 19474230 TI - Prevalence and distribution of permanent canine agenesis in dental paediatric and orthodontic patients in Hungary. AB - Non-syndromic permanent canine agenesis, or combined with agenesis, or developmental absence of other tooth types, has occasionally been described in the literature, but isolated forms are rarely observed. The purpose of the present retrospective radiographic study was to provide data on the prevalence and distribution of permanent canine agenesis in the Hungarian population. Dental panoramic tomograms and the medical history data of 4417, 6- to 18-year-old children (average age 12 years, male-to-female ratio 1:1), who presented for treatment at the Department of Paediatric Dentistry and Orthodontics of the Semmelweis University Budapest, Hungary, were examined. Patients with systemic diseases were excluded. Chi-square and Fisher's tests were performed to determine statistical significance at a level of P < 0.05. Thirteen subjects had permanent canine agenesis. The overall prevalence was 0.29 per cent. The prevalence of permanent canine agenesis was 0.27 per cent in the maxilla and 0.09 per cent in the mandible (P < 0.01). The male-to-female ratio was 1:2.2. Dental anomalies associated with permanent canine agenesis were found: 11 patients had retention of the primary canines, 10 other types of agenesis of the permanent teeth, one a primary supernumerary tooth, one a supernumerary cusp, and nine occlusal disturbances. PMID- 19474231 TI - Self-care strategies and barriers among kidney transplant recipients: a qualitative study. AB - OBJECTIVES: We investigated kidney transplant recipients' self-reported levels of exercise and fluid intake. We also examined attitudes about, barriers to undertaking, and strategies used to initiate and maintain adequate self-care for fluid intake, exercise and dietary practices. METHODS: A qualitative approach was used and supplemented by quantitative data to examine self-care among kidney transplant recipients (n = 82), including a semi-structured interview and survey of physical activity. RESULTS: One-third of patients (33%) reported drinking the recommended 3 L of fluid each day. However, the majority (60%) reported not receiving this or any specific fluid intake recommendation. Twenty percent reported engaging in moderate to regular physical activity while 78% were sedentary. However, many reported that clinicians did not specify the amount of exercise (39%) or did not discuss exercise (15%). Attitudes towards fluid intake, exercise and maintaining a low-salt diet were mostly positive; patients expressed relatively more negative attitudes towards maintaining a low-cholesterol diet. Major barriers to fluid intake were not feeling thirsty, difficulty breaking the habit of limiting fluid intake formed while on dialysis, feeling full and limited access to fluids. Patients devised creative strategies to initiate and maintain appropriate hydration, physical activity and dietary levels, including intentionally drinking when not thirsty, modifying the environment, tracking intake and relying on social supports. CONCLUSIONS: Few kidney recipients practiced optimal self-care for fluid intake or physical activity. Most patients encountered barriers to self-care that should be ameliorated to assist patients with managing their transplant. Understanding barriers and strategies is essential for developing educational interventions. PMID- 19474232 TI - Cascading crises, resilience and social support within the onset and development of multiple chronic conditions. AB - OBJECTIVE: To describe and better understand adults' responses to the onset, accrual and influence of multiple chronic conditions and to social support in adapting to consequent difficulties. METHODS: Qualitative study of 33 adults with multiple chronic illnesses randomly sampled from an urban primary care clinic. Semi-structured interviews targeted retrospective accounts of illness onset, consequent loss, as well as current accounts of social support and adaptation. All interviews were audio-recorded, professionally transcribed and analysed according to established phenomenological procedures. RESULTS: Participants' responses revealed illness onset as a virtual cascade of medical, emotional and social hardships, leading to loss and subsequent adaptation through personal resilience and particularly, available social support. Participants also described patterns of adaptation punctuated by the felt need and rewards of providing care to others. DISCUSSION: The experience of multiple chronic illnesses has a distinct pattern of development and consequence, involving challenges to personal identity and the benefits of social support from and to others. Our results suggest that programmes addressing the needs of persons with multiple chronic conditions might tailor interventions in ways that maximally address their unique challenges. PMID- 19474233 TI - The lived experience of hope among parents of a child with Duchenne muscular dystrophy: perceiving the human being beyond the illness. AB - OBJECTIVES: Duchenne muscular dystrophy (DMD) is genetically determined, progressive and incurable. Our study's primary objective was to describe the lived experience of hope among parents of a child with DMD. METHODS: Semi structured interviews were conducted with 12 parents having a child with DMD. A qualitative/ phenomenological approach was utilized to analyse the essential aspects of this experience. RESULTS: We show that the experience of parental hope emerges from the cognitive appraisal of DMD. The child's illness can be perceived in three ways: as a severe loss, a call to adapt or a way to rediscover the child. Each of these appraisals leads to different ways of hoping. Parents can hope for a cure, the child's well-being or to see their child becoming a whole person. Hope can help parents absorb the initial crisis, sustain their adaptation or prepare for the fatal outcome. DISCUSSION: Previous research has demonstrated that cognitive appraisal plays a central role in psychosocial adaptation to illness. Our research indicates that perception can also shape the nature of hope and suggests that health professionals should pay particular attention to the nature of parental hope. The fabric of parental hope can give an indication of how parents are coping and adjusting. PMID- 19474234 TI - Future directions for investigation of fatigue in chronic hepatitis C viral infection. AB - Fatigue is a common and often debilitating symptom for people living with chronic hepatitis C viral infection. Numerous published reports in the past decade have attempted to address the nature and aetiology of fatigue in chronic hepatitis C; however, this field is plagued with lack of clarity about how hepatitis C virus (HCV)-related fatigue occurs and when it is experienced by the infected person. Consequently, both patients and clinicians alike are unclear about how to mediate or prevent the negative consequences of HCV-related fatigue. In the following article, the authors identify areas of ambiguity and incongruity that have evolved primarily from the underlying assumptions and methodological decisions of researchers in the field of HCV-related fatigue. Research related to fatigue in chronic illness is drawn upon to suggest future directions for investigations and interventions in the field of HCV-related fatigue. Future research needs to move beyond the subjective symptomatology of HCV-related fatigue and begin to account for the multidimensional and contextualised nature of the fatigue experience. PMID- 19474235 TI - The utility of the Necessity--Concerns Framework in explaining treatment non adherence in four chronic illness groups in Italy. AB - OBJECTIVE: To translate the Beliefs about Medicines Questionnaire (BMQ) into Italian and explore the utility of the Necessity-Concerns Framework in explaining treatment non-adherence in four chronic illness groups in Italy. METHODS: 449 patients with chronic illness (depression, asthma, diabetes and cardiac disease) were approached at outpatient clinics in Turin and asked to complete Italian translations of the BMQ and the Medication Adherence Report Scale. RESULTS: 427 patients consented to participate in the study. The BMQ demonstrated good internal consistency, with Cronbach's alphas of 0.78 (Necessity subscale) and 0.72 (Concerns subscale). Participants were divided into four attitudinal groups based on their responses to the BMQ: 59% Accepting (high Necessity, low Concerns), 29% ambivalent (high Necessity, high Concerns), 8% Indifferent (low Necessity, low Concerns) and 4% Skeptical (low Necessity, high Concerns). Those in the Accepting group reported the highest adherence to medication and those in the Skeptical group the lowest (p50.01). DISCUSSION: The BMQ has been successfully translated and validated in Italian. This study provides support for the Necessity-Concerns Framework in explaining medication non-adherence in chronic illness. Interventions that address low perceived need for treatment and concerns about potential adverse effects of treatment are likely to facilitate optimal use of medicines. PMID- 19474236 TI - Will healthcare reform actually occur in the US? AB - Healthcare in the US is currently in a state of chaos. Not only does a large percentage of the population lack health coverage, but overall we are increasingly paying more and more for what in comparison to other countries is a decreasing quality of healthcare. This article describes a few of the factors that compose the context both of current healthcare strategies in the US and of barriers to the creation of a true healthcare system. Accomplishing this goal will require unprecedented bipartisan cooperation of both the Obama administration and Congress. PMID- 19474237 TI - Will healthcare reform actually occur in the US? PMID- 19474238 TI - Will this time be different? PMID- 19474239 TI - Homeopathic Preparations of Quartz, Sulfur and Copper Sulfate Assessed by UV Spectroscopy. AB - Homeopathic preparations are used in homeopathy and anthroposophic medicine. Although there is evidence of effectiveness in several clinical studies, including double-blinded randomized controlled trials, their nature and mode of action could not be explained with current scientific approaches yet. Several physical methods have already been applied to investigate homeopathic preparations but it is yet unclear which methods are best suited to identify characteristic physicochemical properties of homeopathic preparations. The aim of this study was to investigate homeopathic preparations with UV-spectroscopy. In a blinded, randomized, controlled experiment homeopathic preparations of copper sulfate (CuSO(4); 11c-30c), quartz (SiO(2); 10c-30c, i.e., centesimal dilution steps) and sulfur (S; 11*-30*, i.e., decimal dilution steps) and controls (one time succussed diluent) were investigated using UV-spectroscopy and tested for contamination by inductively coupled plasma mass spectrometry (ICP-MS). The UV transmission for homeopathic preparations of CuSO(4) preparations was significantly lower than in controls. The transmission seemed to be also lower for both SiO(2) and S, but not significant. The mean effect size (95% confidence interval) was similar for the homeopathic preparations: CuSO(4) (pooled data) 0.0544% (0.0260-0.0827%), SiO(2) 0.0323% (-0.0064% to 0.0710%) and S 0.0281% ( 0.0520% to 0.1082%). UV transmission values of homeopathic preparations had a significantly higher variability compared to controls. In none of the samples the concentration of any element analyzed by ICP-MS exceeded 100 ppb. Lower transmission of UV light may indicate that homeopathic preparations are less structured or more dynamic than their succussed pure solvent. PMID- 19474240 TI - Meta-analysis of the related nutritional supplements dimethyl sulfoxide and methylsulfonylmethane in the treatment of osteoarthritis of the knee. AB - Dimethyl sulphoxide and methylsulfonylmethane are two related nutritional supplements used for symptomatic relief of osteoarthritis (OA). We conducted a meta-analysis to evaluate their efficacy in reducing pain associated with OA. Randomized or quasi-randomized controlled trials (RCTs), identified by systematic electronic searches, citation tracking and searches of clinical trial registries, assessing these supplements in osteoarthritis of any joint were considered for inclusion. Meta-analysis, based on difference in mean pain related outcomes between treatment and comparator groups, was carried out based on a random effect model. Seven potential trials were identified of which three RCTs, two DMSO and one MSM (total N = 326 patients) were eligible for inclusion. All three trials were considered high methodological quality. A significant degree of heterogeneity (chi(2) = 6.28, P = .043) was revealed. Two studies demonstrated statistically significant (but not clinically relevant) reduction in pain compared with controls; with one showing no group difference. The meta-analysis confirmed a non significant reduction of pain on visual analogue scale of 6.34 mm (SE = 3.49, 95% CI, -0.49, 13.17). The overall effect size of 1.82 was neither statistically nor clinically significant. Current evidence suggests DMSO and MSM are not clinically effective in the reduction of pain in the treatment of OA. No definitive conclusions can currently be drawn from the data due to the mixed findings and the use of inadequate dosing periods. PMID- 19474241 TI - Dejian mind-body intervention on depressive mood of community-dwelling adults: a randomized controlled trial. AB - The present study evaluated the effectiveness of a short-term mind-body intervention program on improving the depressive mood of an adult community sample. Forty adult volunteers with various degrees of depressive mood were randomly assigned to the experimental group (Dejian Mind-Body Intervention, DMBI) and control group (Cognitive-Behavioral Therapy, CBT). For each group, a total of four 90-min weekly sessions were conducted. Treatment-related changes were measured using the Beck Depression Inventory (BDI-II), an electroencephalographic indicator of positive affect (i.e., prefrontal activation asymmetry), and self report ratings on physical health. Results indicated that both the DMBI and the CBT group demonstrated significant reduction in depressive mood. However, among individuals with moderate to severe depressive mood at baseline, only those in the DMBI but not the CBT group showed significant reduction in depressive mood. Besides, only the DMBI group demonstrated a significant increase in prefrontal activation asymmetry, suggesting increase in positive affect. While most psychological therapies for depressive mood normally take several months to show treatment effect, the present findings provided initial data suggesting that the DMBI was effective in improving depressive mood of community adults after 1 month of training. PMID- 19474242 TI - Transduction of vertebrate cells with Spodoptera exigua multiple nucleopolyhedrovirus F protein-pseudotyped gp64-null Autographa californica multiple nucleopolyhedrovirus. AB - Budded virions of the baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) can enter a variety of non-host cells. The capacity of GP64, AcMNPV's endogenous envelope fusion protein, and SeF, the fusion protein from a gp64(-) baculovirus, to mediate baculovirus entry into vertebrate cells was examined by comparing the transduction efficiencies of engineered AcMNPV variants with either of the two envelope proteins into 17 vertebrate cell lines. At an m.o.i. of 500, GP64-expressing viruses transduced all cell lines with varying efficiencies. Transduction efficiencies of SeF-pseudotyped gp64-null AcMNPV into all cell lines were lower than those of GP64-expressing viruses, and were undetectable in seven cell lines. At an m.o.i. of 50, transduction of all mammalian cell lines transducible by the SeF-pseudotyped gp64-null AcMNPV at an m.o.i. of 500 was no longer detectable. An amplifiable SeF-pseudotyped gp64-null AcMNPV vector with greatly reduced tropism for vertebrate cells may have applications in engineering AcMNPV for targeted transduction. PMID- 19474243 TI - Drosophila A virus is an unusual RNA virus with a T=3 icosahedral core and permuted RNA-dependent RNA polymerase. AB - The vinegar fly, Drosophila melanogaster, is a popular model for the study of invertebrate antiviral immune responses. Several picorna-like viruses are commonly found in both wild and laboratory populations of D. melanogaster. The best-studied and most pathogenic of these is the dicistrovirus Drosophila C virus. Among the uncharacterized small RNA viruses of D. melanogaster, Drosophila A virus (DAV) is the least pathogenic. Historically, DAV has been labelled as a picorna-like virus based on its particle size and the content of its RNA genome. Here, we describe the characterization of both the genome and the virion structure of DAV. Unexpectedly, the DAV genome was shown to encode a circular permutation in the palm-domain motifs of the RNA-dependent RNA polymerase. This arrangement has only been described previously for a subset of viruses from the double-stranded RNA virus family Birnaviridae and the T=4 single-stranded RNA virus family Tetraviridae. The 8 A (0.8 nm) DAV virion structure computed from cryo-electron microscopy and image reconstruction indicates that the virus structural protein forms two discrete domains within the capsid. The inner domain is formed from a clear T=3 lattice with similarity to the beta-sandwich domain of tomato bushy stunt virus, whilst the outer domain is not ordered icosahedrally, but forms a cage-like structure that surrounds the core domain. Taken together, this indicates that DAV is highly divergent from previously described viruses. PMID- 19474244 TI - Phylogeography and molecular epidemiology of hepatitis C virus genotype 2 in Africa. AB - Understanding the origin and nature of hepatitis C virus (HCV) genetic diversity is critical for improving treatment and vaccine design, and such diversity is the sole source of information about the virus' epidemic history prior to its identification 20 years ago. In this paper, we study the molecular epidemiology of HCV genotype 2 in its region of endemic origin, west and central Africa. Our analysis includes 56 new and highly diverse HCV isolates sampled from infected individuals in Guinea-Bissau. By combining phylogenetic, geographical and epidemiological information, we find a previously unappreciated geographical structure in the diversity of HCV genotype 2, pointing to a history of eastwards spatial spread from the west African coast to Cameroon that took place over several centuries. Molecular clock analysis dates the common ancestor of HCV in Guinea-Bissau to 1470 (1414-1582). The phylogenetic position of isolates from Madagascar and Martinique suggests a role for the historical slave trade in the global dissemination of HCV and of the epidemic subtypes 2a and 2c. Coalescent based estimates of epidemic growth indicate a rapid 20th-century spread of HCV genotype 2 in Cameroon that is absent in Guinea-Bissau. We discuss this contrast in the context of possible parenteral HCV exposure during public-health campaigns undertaken during the colonial era. PMID- 19474245 TI - The 3' untranslated region of cucumber mosaic virus (CMV) subgroup II RNA3 arose by interspecific recombination between CMV and tomato aspermy virus. AB - Recombination in single-stranded RNA viruses is one of the principal mechanisms responsible for their evolution. Here we show, using a variety of different methods, that the 3' untranslated region (3'UTR) of subgroup II strains of cucumber mosaic virus [CMV(II)] is related more closely to that of tomato aspermy virus (TAV) than to those of CMV(I) strains. These results suggest that the CMV(II) 3'UTR arose by interspecific CMV/TAV recombination. The putative crossover is close to the 5' end of the 3'UTR, at a recombination hot spot previously observed in short time-frame experiments. The CMV(II) strains show divergence from TAV at specific points along the 3'UTR that most probably indicate adaptive changes due to natural selection. Thus, for the large majority of CMV(II) strains examined, the 3'UTR has two discrete regions, W (nt 1902-1971) and Y (nt 2126-2184), that are more similar to the corresponding regions of TAV than to those of CMV(I) strains. PMID- 19474246 TI - A unicellular algal virus, Emiliania huxleyi virus 86, exploits an animal-like infection strategy. AB - Emiliania huxleyi virus 86 (EhV-86) belongs to the family Phycodnaviridae, a group of viruses that infect a wide range of freshwater and marine eukaryotic algae. Phycodnaviridae is one of the five families that belong to a large and phylogenetically diverse group of viruses known as nucleocytoplasmic large dsDNA viruses (NCLDVs). To date, our understanding of algal NCLDV entry is based on the entry mechanisms of members of the genera Chlorovirus and Phaeovirus, both of which consist of non-enveloped viruses that 'inject' their genome into their host via a viral inner-membrane host plasma membrane fusion mechanism, leaving an extracellular viral capsid. Using a combination of confocal and electron microscopy, this study demonstrated for the first time that EhV-86 differs from its algal virus counterparts in two fundamental areas. Firstly, its capsid is enveloped by a lipid membrane, and secondly, EhV-86 enters its host via either an endocytotic or an envelope fusion mechanism in which an intact nucleoprotein core still encapsulated by its capsid is seen in the host cytoplasm. Real-time fluorescence microscopy showed that viral internalization and virion breakdown took place within the host on a timescale of seconds. At around 4.5 h post infection, virus progeny were released via a budding mechanism during which EhV 86 virions became enveloped with host plasma membrane. EhV-86 therefore appears to have an infection mechanism different from that employed by other algal NCLDVs, with entry and exit strategies showing a greater analogy to animal-like NCLDVs. PMID- 19474247 TI - Virulence and pathophysiology of the Congo Basin and West African strains of monkeypox virus in non-human primates. AB - Monkeypox virus is divided into Congo Basin and West African strains. The virulence and pathophysiology of two strains, Zr-599 (a Congo Basin monkeypox virus) and Liberia (a West African monkeypox virus), were evaluated in non-human primates. Four monkeys were infected by the subcutaneous (SC) and two by the intranasal (IN) inoculation routes for Zr-599 and Liberia at a dose of 10(6) p.f.u. One monkey in the Liberia/SC group was demonstrated to be co-infected with Gram-positive cocci and was excluded from analyses. Infections in three of the four Zr-599/SC monkeys and in one of the three Liberia/SC monkeys were fatal. Virus genome levels in blood in the Zr-599/SC monkeys were approximately 10 times higher than those in the Liberia/SC monkeys. Zr-599 affected respiratory, genito urinary and gastrointestinal tract organs more severely than Liberia. Zr-599 was more virulent than Liberia and one of the factors might be the difference in organ tropism. PMID- 19474248 TI - Effects of dicer-like endoribonucleases 2 and 4 on infection of Arabidopsis thaliana by cucumber mosaic virus and a mutant virus lacking the 2b counter defence protein gene. AB - In tobacco and Nicotiana benthamiana, limited cross-protection against cucumber mosaic virus strain Fny (Fny-CMV) was provided by prior inoculation with a deletion mutant lacking the 2b silencing-suppressor protein gene (Fny CMVDelta2b). Cross-protection by Fny-CMVDelta2b did not result from induction of systemic RNA silencing. We investigated whether protection occurs through induction of localized RNA silencing by using Arabidopsis thaliana plants harbouring mutations in genes encoding the dicer-like (DCL) endoribonucleases 2, 3 and 4 involved in antiviral silencing. In wild-type A. thaliana (Col-0) plants, Fny-CMVDelta2b was symptomless and cross-protected against Fny-CMV infection. Cross-protection by Fny-CMVDelta2b against Fny-CMV infection was not abolished in dcl2, dcl3 or dcl4 mutant plants and was strongest in dcl2/4 double mutants, although in these plants and in dcl4 mutants, Fny-CMVDelta2b replicated to high levels and induced strong symptoms. The results suggest that Fny-CMVDelta2b/Fny CMV cross-protection is not completely dependent on RNA silencing and also involves competition between these viruses. PMID- 19474249 TI - Differential virulence mechanisms of infectious hematopoietic necrosis virus in rainbow trout (Oncorhynchus mykiss) include host entry and virus replication kinetics. AB - Host specificity is a phenomenon exhibited by all viruses. For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), differential specificity of virus strains from the U and M genogroups has been established both in the field and in experimental challenges. In rainbow trout (Oncorhynchus mykiss), M IHNV strains are consistently more prevalent and more virulent than U IHNV. The basis of the differential ability of these two IHNV genogroups to cause disease in rainbow trout was investigated in live infection challenges with representative U and M IHNV strains. When IHNV was delivered by intraperitoneal injection, the mortality caused by U IHNV increased, indicating that the low virulence of U IHNV is partly due to inefficiency in entering the trout host. Analyses of in vivo replication showed that U IHNV consistently had lower prevalence and lower viral load than M IHNV during the course of infection. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate immune-related genes such as Mx-1. This suggests that the higher virulence of M IHNV is not due to suppression of the immune response in rainbow trout. Taken together, the results support a kinetics hypothesis wherein faster replication enables M IHNV to rapidly achieve a threshold level of virus necessary to override the strong host innate immune response. PMID- 19474250 TI - NS4A regulates the ATPase activity of the NS3 helicase: a novel cofactor role of the non-structural protein NS4A from West Nile virus. AB - Using constructs that encode the individual West Nile virus (WNV) NS3helicase (NS3hel) and NS3hel linked to the hydrophilic, N-terminal 1-50 sequence of NS4A, we demonstrated that the presence of NS4A allows NS3hel to conserve energy in the course of oligonucleotide substrate unwinding. Using NS4A mutants, we also determined that the C-terminal acidic EELPD/E motif of NS4A, which appears to be functionally similar to the acidic EFDEMEE motif of hepatitis C virus (HCV) NS4A, is essential for regulating the ATPase activity of NS3hel. We concluded that, similar to HCV NS4A, NS4A of WNV acts as a cofactor for NS3hel and allows helicase to sustain the unwinding rate of the viral RNA under conditions of ATP deficiency. PMID- 19474251 TI - Magnetic resonance imaging evaluation of mandibular condyle bone marrow and temporomandibular joint disc signal intensity in anaemia patients. AB - OBJECTIVES: To compare the signal intensity (SI) of mandibular condyle bone marrow (MCBM) and the temporomandibular joint (TMJ) disc in patients with chronic anaemia and healthy subjects, and to investigate the relationships between bone marrow changes, age, types of anaemia and severity of anaemia. METHODS: MRIs of 18 patients with chronic anaemia were compared with those of 12 healthy subjects. The SI of MCBM and the TMJ disc were quantitatively evaluated. The SI of the grey matter (GM), white matter (WM) and the lateral pterygoid muscle were also investigated. Relationships between age, MCBM and TMJ disc signal-intensities and anaemia severity, and correlations between the groups, were analysed. RESULTS: The mean MCBM SI was lower in anaemia patients (including both subgroups and also separately) than in healthy subjects (P < 0.05). No statistical significance was found for GM, WM and the muscle SI between the anaemia patients and healthy patient group (P > 0.05). No statistical significance was found between the groups with respect to the anterior band, whereas the mean SI value of the posterior band in the study group was significantly lower than in healthy subjects (P < 0.05). There were no correlations between age and MCBM SI, or between anaemia severity and MCBM SI. CONCLUSIONS: Anaemia may cause bone marrow alterations without any internal derangement. Patients with chronic anaemia exhibit lower mandibular condyle bone marrow and posterior band SI than healthy subjects. PMID- 19474252 TI - Reliability of mandibular cortical index and mandibular bone mineral density in the detection of osteoporotic women. AB - OBJECTIVES: Measuring the bone mineral density (BMD) of the femur and lumbar vertebrae has been the traditional method for determining osteoporosis in women. In this study, we tried to determine the relationships between mandibular dual energy X-ray absorptiometry (m-DXA) values obtained with a new methodology, mandibular cortical index (MCI), total BMD values of the femur and lumbar vertebrae in 80 women with osteoporosis determined by DXA in conformity with T score thresholds, as defined by the World Health Organization (WHO). METHODS: m DXA and panoramic radiography were performed on 80 women with osteoporosis. m-DXA was calculated by manual analysis of DXA scans. MCI was determined by the appearance of the mandibles on panoramic radiographs. DXA measurements of the skeletal BMD (femur and lumbar vertebras) and MCI values were also calculated. Correlations between these variables were assessed. RESULTS: Although there were no correlations between skeletal BMD (total BMD values of the femur and lumbar vertebras) and mandibular measurements (mDXA and MCI), we found that there was a significant correlation between the skeletal BMDs (r = 0.355, P = 0.001). CONCLUSIONS: It is concluded that no significant correlations were found between the mandibular and non-mandibular measures in women with osteoporosis. PMID- 19474253 TI - Comparison of reliability in anatomical landmark identification using two dimensional digital cephalometrics and three-dimensional cone beam computed tomography in vivo. AB - OBJECTIVES: To compare reliability for landmark identification on patient images from three-dimensional (3D) cone beam CT (CBCT) and digital two-dimensional (2D) lateral cephalograms. METHODS: Ten lateral cephalometric digital radiographs and their corresponding CBCT images were randomly selected. 27 observers digitally identified 27 landmarks in both modes. The x- and y-coordinates for each landmark, indicating the horizontal and vertical positions, were analysed for interobserver reliability by comparing each measurement to the best estimate of the true value. Intraobserver reliability was also assessed. Linear models and intraclass correlation coefficients (ICCs) were used for analyses. RESULTS: For interobserver reliability, the following locations were farther from the best estimate for 2D than 3D: x-location in subspinale (A-point), anterior tip of the nasal spine (ANS), L1 lingual gingival border and L1 root; y-location in porion, ramus point and orbitale; x- and y-locations in basion, condylion, midramus, sigmoid notch and U6 occlusal. 3D y-locations were farther in the gonion, L1 tip, sella and U1 tip. For intraobserver reliability, 2D locations were farther in y locations in orbitale and sigmoid notch, and both x- and y-locations in basion. 3D locations were farther in the x-location in U1 labial gingival border and y locations in L1 tip, L6 occlusal, menton and sella. For intraobserver ICCs, greater variations in 2D than 3D included: A-point, ANS, midramus, orbitale, ramus point, sigmoid notch and U1 root. CONCLUSIONS: 3D imaging, as in CBCT, allows for overall improved interobserver and intraobserver reliability in certain landmarks in vivo when compared with two-dimensional images. PMID- 19474254 TI - Evaluation of distracted mandibular bone using computed tomography scan and ultrasonography: technical note. AB - OBJECTIVES: Distraction osteogenesis is considered an important reconstruction armamentarium in the management of mandibular deformities and deficiency disorders. The duration of the consolidation period is still a debatable issue among the clinicians. Evaluation of the newly formed bone is the cornerstone for terminating the consolidation period safely. The aim of this study is to find a more conservative protocol for the evaluation of callus distraction by monitoring bone healing using two different examination tools: ultrasonography and dental CT. METHODS: Four adult patients (three women and one man) underwent mandibular distraction (using two intraoral and two extraoral devices). The latency period was 5-7 days and the distraction was at a rate of 2 mm per day, with 12-14 weeks of consolidation. All patients were evaluated during activation, 3 months, 6 months and 1 year post-distraction. Evaluation included clinical examination, plain radiographs, CT and ultrasonography examinations. RESULTS: Ultrasonographic examination of the healing callus revealed four different phases of maturation. These phases were similar to the degree of tissue calcification as measured by CT. Tissue density across the distraction wound at the time of distractor removal (12-14 weeks) was equal to or less than one-third of normal bone density. CONCLUSIONS: Clinical monitoring of mandibular distraction wounds can be successfully achieved through frequent use of ultrasonographic examinations. Standardization of ultrasonography based on CT findings will expand the reliability of ultrasound in monitoring callus maturation. An algorithm for evaluation of distraction wound healing is suggested. PMID- 19474255 TI - Application of fractal analysis in hyperparathyroidism. AB - OBJECTIVES: Primary hyperparathyroidism (HPT) is a condition caused by an overproduction of parathormone, in excess of the amount required by the body. Its most common cause is a parathyroid gland adenoma and parathyroidectomy is currently the only curative treatment for primary HPT. We present a case history of a 65-year-old patient who was diagnosed with primary HPT after the recognition of dental problems. METHODS: Dental complaints of the patient alerted the dentists, and the patient was referred for further medical evaluation. In addition to his current medical status, his medical records including the biochemical parameters of bone metabolism recorded between 2001 and 2006 were reviewed. The panoramic films of the patient obtained between 1997 and 2008 were also assessed with the fractal analysis method. RESULTS: After consideration of the radiographical, biochemical and clinical evaluations of the patient, the final diagnosis was made as hyperparathyroid adenoma and surgical removal was scheduled. Soon after surgery, alkaline phosphatase, calcium and intact parathormone levels returned to normal. The fractal analysis value of the mandibular alveolar bone also increased. CONCLUSIONS: Dentoalveolar changes observed in HPT include alveolar bone demineralization. The fractal dimension (FD) analysis of the bone tissue has been introduced as an alternative method to investigate the quality of the alveolar bone. FD values of the patient showed osteoporotic bone characteristics between 1997 and 2006 until the date of parathyroidectomy. Mandibular bone FD analyses revealed a prominent development, which was also observed in dual energy X-ray absorptiometry values. PMID- 19474256 TI - Acute lymphoblastic leukaemia: an unusual radiological presentation. AB - A 14-year-old female patient attended Bristol Dental Hospital for an oral screening prior to undergoing a bone marrow transplant as treatment for her acute lymphoblastic leukaemia. Maxillofacial radiographs revealed multiple, well defined, non-corticated radiolucent lesions throughout the vault of her skull and mandible. These radiological features (coupled with the patient's age) would have correlated with a diagnosis of Langerhans cell histiocytosis. However, a previous bone marrow biopsy confirmed that the patient did indeed have acute lymphoblastic leukaemia. The lytic lesions were present throughout her entire skeletal frame and had previously led to episodes of leg and abdominal pain. We feel that this radiological presentation of leukaemia needs to be reported as these features could easily have been confused with other haematological or even malignant conditions. PMID- 19474257 TI - Gorham's massive osteolysis of the mandible - a progressive radiographic presentation. AB - Massive osteolysis is well known under the synonyms Gorham's disease, vanishing bone disease and phantom bone disease. It is a rare condition of unknown aetiology and results in the progressive destruction of bony structures. Only a few cases have been reported in the jaws. Considering the rarity of the condition, we report here an interesting and unique case of massive osteolysis of the lower jaw that initially affected the mandibular basal and alveolar bone, and subsequently involved the rami and the condyles. The clinical and radiological findings were consistent with the criteria for the diagnosis of Gorham's massive osteolysis. PMID- 19474258 TI - Two maxillary lesions containing bony/calcified shells. AB - Because of the close anatomical relationship between the maxillary sinus and the adjacent dental region, determining the primary site of cysts in these regions can be a diagnostic dilemma. In this article, two cases with similar radiological findings are presented. These cases had lesions involving the maxillary sinus and the adjacent alveolar process; the lesions were surrounded with egg-shaped, linear opacities. Diagnoses of a residual radicular cyst in one case and a calcified mucocoele (which is very rare) in the other case were predicted with the help of radiological findings and were confirmed surgically and histopathologically. PMID- 19474259 TI - Cone beam computed sialography of sialoliths. AB - Cone beam CT is an emerging imaging modality used in maxillofacial imaging. This paper describes the use of cone beam sialography in two patients with salivary gland obstruction. In both cases, the obstruction was identified. The dose is comparable with conventional fluoroscopic techniques and has the advantage that the data may be viewed in a series of fine slices and in three dimensions, which may help in diagnosis and further management of the patient. PMID- 19474260 TI - Is it time to set a Hounsfield standard? PMID- 19474261 TI - Antibodies specific for the Hia adhesion proteins of nontypeable Haemophilus influenzae mediate opsonophagocytic activity. AB - The Hia autotransporter proteins are highly immunogenic surface adhesins expressed by nontypeable Haemophilus influenzae (NTHI). The objective of our study was to assess the opsonophagocytic activity of anti-Hia antibodies against homologous and heterologous NTHI. A segment of the hia gene that encodes a surface-exposed portion of the H. influenzae strain 11 Hia protein was cloned into a pGEMEX-2 expression vector. Escherichia coli JM101 was transformed with the resulting pGEMEX-Hia BstEII del recombinant plasmid, and recombinant fusion protein was recovered. An immune serum against recombinant GEMEX-Hia (rGEMEX-Hia) mediated killing of the homologous NTHI strain 11 at a 1:160 titer and five heterologous Hia-expressing strains at titers of > or =1:40. Immune serum did not mediate killing of two Hia-knockout strains whose hia genes were inactivated but did mediate killing of one knockout strain at a high titer after the strain was transformed with a plasmid containing the hia gene. Immune serum did not mediate killing of HMW1/HMW2-expressing NTHI strains, which do not express the Hia adhesin. However, when two representative HMW1/HMW2-expressing strains were transformed with the plasmid containing the hia gene, they expressed abundant Hia and were susceptible to killing by the immune serum. Immune serum did not mediate killing of HMW1/HMW2-expressing strains transformed with the plasmid without the hia gene. Our results demonstrate that the Hia proteins of NTHI are targets of opsonophagocytic antibodies and that shared epitopes recognized by such antibodies are present on the Hia proteins of unrelated NTHI strains. These data argue for the continued investigation of the Hia proteins as vaccine candidates for the prevention of NTHI disease. PMID- 19474262 TI - Early detection of human immunodeficiency virus type 1-specific B-lymphocyte derived antibodies in a high-risk population. AB - Diagnosis of acute human immunodeficiency virus (HIV) infection, a key driver of the HIV epidemic, remains a public health challenge. The PlasmAcute technology offers an opportunity to detect early anti-HIV antibody responses. B lymphocytes (B cells) were isolated from the blood of seronegative miners in South Africa by using the PlasmAcute method. B-cell lysates and paired sera were tested for anti HIV-1 antibodies by two different enzyme-linked immunosorbent assays; immunoreactivity was confirmed by Western blotting. All volunteers were tested for HIV type 1 (HIV-1) viral load, p24 antigen, and CD4 count. Sera from HIV seronegative men who had positive viral loads and were positive for p24 antigen were retested for anti-HIV antibodies after immune complex dissociation. Anti-HIV antibodies were detected in lysates from 16/259 subjects without immunoreactivity in paired sera. Four subjects, one of whom had a positive viral load initially, subsequently seroconverted. Six subjects showed transient anti-HIV-1 antibodies in the lysates and tested negative for all markers at the follow-up. Five subjects without follow-up data initially had lysate-positive/serum-negative samples, and these cases were classified as inconclusive. One subject had lysate antibodies and a detectable viral load but was seronegative at follow-up. In conclusion, lysate-derived anti-HIV-1 B-cell antibodies can be detected prior to seroconversion and earlier than or contemporary with HIV-1 RNA detection. PMID- 19474263 TI - Immunological profiles of Bos taurus and Bos indicus cattle infested with the cattle tick, Rhipicephalus (Boophilus) microplus. AB - The cattle tick, Rhipicephalus (Boophilus) microplus, is a major threat to the improvement of cattle production in tropical and subtropical countries worldwide. Bos indicus cattle are naturally more resistant to infestation with the cattle tick than are Bos taurus breeds, although considerable variation in resistance occurs within and between breeds. It is not known which genes contribute to the resistant phenotype, nor have immune parameters involved in resistance to R. microplus been fully described for the bovine host. This study was undertaken to determine whether selected cellular and antibody parameters of the peripheral circulation differed between tick-resistant Bos indicus and tick-susceptible Bos taurus cattle following a period of tick infestations. This study demonstrated significant differences between the two breeds with respect to the percentage of cellular subsets comprising the peripheral blood mononuclear cell population, cytokine expression by peripheral blood leukocytes, and levels of tick-specific immunoglobulin G1 (IgG1) antibodies measured in the peripheral circulation. In addition to these parameters, the Affymetrix bovine genome microarray was used to analyze gene expression by peripheral blood leukocytes of these animals. The results demonstrate that the Bos indicus cattle developed a stabilized T-cell mediated response to tick infestation evidenced by their cellular profile and leukocyte cytokine spectrum. The Bos taurus cattle demonstrated cellular and gene expression profiles consistent with a sustained innate, inflammatory response to infestation, although high tick-specific IgG1 titers suggest that these animals have also developed a T-cell response to infestation. PMID- 19474264 TI - Investigation of different group A immunoassays following one dose of meningococcal group A conjugate vaccine or A/C polysaccharide vaccine in adults. AB - A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a > or = 4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group. PMID- 19474265 TI - Antibody responses to recombinant polyomavirus BK large T and VP1 proteins in young kidney transplant patients. AB - BK virus (BKV)-specific immunity is critical for polyomavirus-associated nephropathy, but antibody responses are incompletely defined. We compared the hemagglutination inhibition assay (HIA) with immunoglobulin G enzyme immunoassays (EIA) to BKV proteins expressed in baculovirus-infected insect cells. N-terminal, internal, and C-terminal domains of the BKV large T antigen (BKLT) were fused to glutathione S-transferase (GST), yielding GST-BKLTD1, GST-BKLTD2, and GST-BKLTD3, respectively. The BKV capsid VP1 was expressed as a GST fusion (BKVP1) or as a native VP1 assembled into viruslike particles (BKVLP). We tested 422 sera from 28 healthy donors (HD), 99 dialysis patients (DP; median age, 15 years; range, 3 to 32 years), and 46 age-matched kidney transplant patients (KTP; median age, 15 years; range, 2 to 33 years). In HD, HIA and BKVLP EIA both yielded a 91.7% seroreactivity, whereas all other EIA responses were lower (BKVP1, 83.3%; BKLTD1, 25%; BKLTD2, 29%; BKLTD3, 40%). HIA titers significantly correlated with EIA levels for BKVLP, BKVP1, and BKLTD1 but not for BKLTD2 or BKLTD3, which were barely above the cutoff. In DP, the seroreactivities of HIA, BKVLP, and BKLTD1 were lower than that in HD (63.6%, 86.9%, and 10.1%, respectively) and they had lower titers (P < 0.001). In KTP, seropositivities for BKVLP, BKVP1, and BKLTD1 were 78%, 50%, and 17%, respectively, but anti-BKVLP levels increased significantly in KTP with viruria and viremia, whereas anti-BKLTD1 levels increased after clearing sustained BKV viremia. In conclusion, anti-BKVLP is equivalent to HIA in HD but is more sensitive to determine the BKV serostatus in DP and KTP. In KTP, anti-BKVLP responds to recent BKV viruria and viremia, whereas anti-BKLTD1 may indicate emerging BKV-specific immune control. PMID- 19474266 TI - Ultra-high-throughput, automated nucleic acid detection of human immunodeficiency virus (HIV) for infant infection diagnosis using the Gen-Probe Aptima HIV-1 screening assay. AB - The early diagnosis of human immunodeficiency virus (HIV) infection in infants is critical to ensure the initiation of treatment before significant immunological compromise. Each year an estimated 300,000 HIV-exposed infants in South Africa require access to tests for the diagnosis of HIV infection. Currently, testing is performed at several facilities by using PCR amplification of HIV DNA at 6 weeks of age by the use of dried blood spots (DBSs) and whole blood (WB). The Gen-Probe Aptima HIV type 1 (HIV-1) screening assay (the Aptima assay) is a qualitative nucleic acid test based on transcription-mediated amplification (TMA), a technology routinely used in blood banks in South Africa. The performance characteristics of Gen-Probe's TMA technology compared well to those of the Roche Amplicor HIV-1 DNA (version 1.5) assay. The sensitivity of the assay with WB and DBS samples was 100%, and the specificities were 99.4% and 99.5% for DBSs and WB, respectively. The detection of HIV by the Aptima assay at greater levels of dilution in samples negative by the comparator assay indicates an improvement in sensitivity by the use of the TMA technology. The ability to process 1,900 samples in a 24-h period on the Tigris instrument makes the Aptima assay an attractive option for high-volume, centralized laboratories. PMID- 19474267 TI - Mupirocin resistance among methicillin-resistant Staphylococcus aureus-colonized patients at admission to a tertiary care medical center. AB - All patients admitted to our tertiary care hospital from 1 December 2007 to 10 June 2008 were screened for methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) nasal colonization, and the isolates were tested for mupirocin susceptibility by using Etest. Mupirocin resistance (MR) was noted to occur in 3.4% of MRSA carriers, and high-level MR was noted to occur in 0.62% of carriers. PMID- 19474268 TI - Confirmation of the first Hong Kong case of human infection by novel swine origin influenza A (H1N1) virus diagnosed using ultrarapid, real-time reverse transcriptase PCR. PMID- 19474269 TI - Detection and genomic characterization of Aichi viruses in stool samples from children in Monastir, Tunisia. AB - Aichi virus has been associated with acute gastroenteritis in adults and children. Stool samples were collected from 788 Tunisian children suffering from diarrhea. Aichi virus was found in 4.1% of the cases. The high proportion of monoinfections and the high frequency of hospitalizations support the role of Aichi virus in pediatric gastroenteritis. PMID- 19474270 TI - Validation of the SPF10 LiPA human papillomavirus typing assay using formalin fixed paraffin-embedded cervical biopsy samples. AB - Lower levels of performance of human papillomavirus (HPV) typing assays in studies using formalin-fixed paraffin-embedded (FFPE) tissue compared to those using exfoliated cervical cells have been reported. The interpretation of current studies is limited by bias in inclusion criteria, sample matching, and methods of cell collection. We aimed to validate FFPE tissue for typing by the use of the SPF(10) LiPA assay, comparing cervical scrapings to punch and cone biopsy specimens. We examined 165 paired cervical scraping and FFPE punch biopsy samples, and 66 paired FFPE punch and cone biopsy samples. HPV typing was performed using the SPF(10) LiPA assay. Kappa statistics were used to measure interrater agreement. The overall agreement with respect to HPV status was 100%. For 74.5% of subjects (kappa = 0.6147), the same numbers of HPV types were detected in scraping and biopsy specimens. The overall positive typing agreement was 95.4% (range, 93.4 to 97.3) for 441 out of 484 individual HPV type analyses. Agreement was good for HPV-39, -42, -43, and -70 (kappa = 0.6506 to 0.7166), excellent for HPV-6, -16, -18, -31, -33, -35, -40, -51, -52, -56, -58, and -66 (kappa = 0.8499 to 0.9665), and absolute for HPV-11, -44, -45, -53, and -68. In 43.9% of cases (kappa = 0.247), the same numbers of HPV types were found in punch and cone biopsy specimens. Overall positive agreement for typing was 86.8% (range, 82.5 to 91.1) for 204 out of 266 individual HPV type analyses. More infections by HPV-18, -33, -51, and -52 were detected in cone specimens. HPV typing by SPF(10) LiPA performed equally well for cervical scraping specimens and standard pathological material. Some viral types are preferentially detected in cone specimens, likely reflecting better sampling of diseased epithelium and endocervix tissue. PMID- 19474271 TI - Calcium-containing phosphate binders: should we CARE-2 avoid them? PMID- 19474272 TI - The association between parathyroid hormone and mortality in dialysis patients is modified by wasting. AB - BACKGROUND: The association between parathyroid hormone (PTH) level and mortality in dialysis patients is controversial. We hypothesized that wasting, a common condition potentially related to adynamic bone disease, modifies the association of PTH with mortality and cardiovascular events (CVE), respectively. METHODS: We analysed data from 1255 diabetic haemodialysis patients, participating in the German Diabetes and Dialysis Study between 1998 and 2004. The patients were stratified by the presence or absence of wasting (albumin 3.8 g/dL; BMI 23 kg/m(2)). Using Cox regression analyses, we calculated the risks of (1) all-cause mortality and (2) CVE according to baseline PTH levels. All analyses were adjusted for age, sex, atorvastatin treatment, duration of dialysis, comorbidity, HbA1c, phosphate, calcium, blood pressure, haemoglobin and C-reactive protein. RESULTS: Patients had a mean age of 66 +/- 8 years, and 54% were male. Among patients without wasting (albumin >3.8 g/dL, n = 586), the risks of death and CVE during 4 years of follow-up significantly increased by 23% and 20% per unit increase in logPTH. Patients in the highest PTH tertile had a 74% higher risk of death (HR(adj) 1.74, 95% CI 1.27-2.40) and a 49% higher risk of CVE (HR(adj) 1.49, 95% CI 1.05-2.11) compared to patients in the lowest PTH tertile. In contrast, no effect was found in patients with wasting. Accordingly, additional analyses in strata of BMI showed that PTH significantly impacted on death and CVE [HR(logPTH)(adj) 1.15 and 1.14, respectively] only in patients without, but not in patients with, wasting. CONCLUSIONS: Wasting modifies the association of PTH with adverse outcomes in diabetic dialysis patients. High PTH levels are of concern in the patients without wasting, while the effect of PTH on mortality is nullified in the patients with wasting. PMID- 19474273 TI - The predictive performance of plasma neutrophil gelatinase-associated lipocalin (NGAL) increases with grade of acute kidney injury. AB - BACKGROUND: In adult cardiac surgery, the predictive value for AKI of neutrophil gelatinase-associated lipocalin (NGAL) appears to have wide variability. The choice of definition of acute kidney injury (AKI) might, at least in part, account for such variability. METHODS: In a prospective study of 100 adult cardiac surgery patients, we assessed the value of postoperative plasma NGAL in predicting AKI according to the degree of severity used for its definition. RESULTS: The predictive value of plasma NGAL varied according to the AKI definition used and was higher for more severe AKI (increase in creatinine >50%: mean AUC-ROC 0.79 +/- 0.01) compared to less severe AKI (>25%: mean AUC-ROC 0.65 +/- 0.02); P = 0.001. The discriminatory ability of NGAL for AKI also increased with increasing RIFLE classes (AUC-ROC R: 0.72, I: 0.79, F: 0.80) or AKIN stages (AUC-ROC 1: 0.75, 2: 0.78, 3: 0.81); P = 0.015. It was highest for the prediction of renal replacement therapy (AUC-ROC: 0.83). CONCLUSIONS: In adult cardiac surgery patients, the predictive value of NGAL increases with grade of AKI. This observation needs to be taken into account when interpreting any future studies of this biomarker. PMID- 19474274 TI - Reduction in urinary excretion of neutrophil gelatinase-associated lipocalin by angiotensin receptor blockers in hypertensive patients. PMID- 19474275 TI - In vitro anti-fibrotic activities of herbal compounds and herbs. AB - BACKGROUND: We recently developed high-throughput assays of inflammation independent anti-fibrotic activities based on TGF-beta1-induced total collagen accumulation and nodule formation in normal rat kidney fibroblasts. METHODS: These assays were applied to examine the anti-fibrotic activities of 21 compounds isolated from plants used in Chinese medicine and methanol extracts of 12 Chinese herbs. Lactate dehydrogenase release assay and cell detachment index were used to monitor cytotoxicity. Changes in fibrogenic molecular markers were observed by reverse transcriptase quantitative polymerase chain reaction and high-content imaging analysis of immunofluorescence. RESULTS: Three flavonoids (quercetin, baicalein and baicalin) and two non-flavonoids (salvianolic acid B and emodin) demonstrated anti-fibrotic activities in both total collagen accumulation and nodule formation assays. The remaining 16 compounds had little anti-fibrotic effect or were cytotoxic. The anti-fibrotic compounds suppressed collagen I expression at both mRNA and protein levels and also variably suppressed alpha smooth muscle actin expression and bromodeoxyuridine incorporation. Methanol extracts of Scutellaria baicalensis Georgi, Salvia miltiorrhiza Bunge and Rheum palmatum L., which are rich sources of baicalein, baicalin, salvianolic acid B and emodin, respectively, also showed in vitro anti-fibrotic activities. CONCLUSIONS: Five herbal compounds and three herbal extracts have in vitro anti fibrotic activities. These data warrant further studies on these anti-fibrotic entities and suggest it a promising strategy to discover new anti-fibrotic drugs by screening more plant materials. PMID- 19474276 TI - Aldosterone, a vasculotoxic agent--novel functions for an old hormone. PMID- 19474277 TI - Diagnosis of pulmonary tuberculosis among dialysis patients by enzyme-linked immunospot assay for interferon-gamma. PMID- 19474278 TI - Not all that itches is uraemic pruritus. PMID- 19474279 TI - Congenital disorders of glycosylation: a rare cause of nephrotic syndrome. AB - Congenital disorders of glycosylation (CDG) are inborn errors of metabolism presenting with multi-system organ involvement due to defective glycosylation of glycoproteins. We report here a case of microcephaly, hypotonia, seizure disorder and severe developmental delay since infancy in whom screening for CDG with transferring isoelectric focussing (TIEF) revealed a type I pattern. Following investigation, the specific defect in glycosylation remains to be identified; hence, a diagnosis of CDG Ix (type unknown) was made. At the age of 15-months the patient developed nephrotic syndrome and renal biopsy indicated a histopathological diagnosis of diffuse mesangial sclerosis on histopathology. Since cases of CDG Ix may often develop hypoalbuminaemia secondary to malabsorption or liver disease, this case highlights the need for additional regular monitoring for glomerular proteinuria, and indicates that a diagnosis of nephrotic syndrome should be considered in all types of CDG. Furthermore, we propose that early treatment with anti-proteinuric agents may be necessary to limit proteinuria and slow disease progression. PMID- 19474280 TI - The role of FGF-23 in CKD patients still needs to be clarified. PMID- 19474281 TI - Ageing mouse kidney--not always the SAME old story. AB - BACKGROUND: As interest in the ageing kidney grows rapidly, more experimental ageing studies are conducted in the field. One of the main obstacles that researchers have to face is that studies in old animals are often less reproducible than in young animals. We have observed that the aged animal's provenance can be an overlooked factor accounting for such experimental heterogeneity. METHODS: Male C57BL/6J mice aged 19-22 months were purchased from four different suppliers. Baseline renal parameters were evaluated by measuring serum urea, serum creatinine and proteinuria. Renal morphology was analysed by quantifying glomerulosclerosis, interstitial fibrosis and amyloid deposits on paraffin sections stained with PAS, Masson trichrome, Sirius red and Congo red. RESULTS: We found normal renal ageing in mice from three sources, but an unexpected renal pathology in mice from one major European supplier. Mice from this supplier had significantly elevated serum urea, creatinine values and an increased urinary protein excretion. Corresponding kidneys displayed massive glomerulosclerosis with evidence of amyloid deposits and increased interstitial fibrosis. CONCLUSIONS: Supplier-dependent differences, such as observed here, can explain irreproducibility of experimental results in renal ageing research. This can be avoided by careful baseline analysis prior to in vivo experiments. PMID- 19474282 TI - Alpha-lipoic acid attenuates cisplatin-induced acute kidney injury in mice by suppressing renal inflammation. AB - BACKGROUND: Cisplatin is a chemotherapeutic agent used in treatment of malignant tumours. However, cisplatin produces various side effects, such as nephrotoxicity, neurotoxicity, emetogenesis and ototoxicity. Inflammation is an important mechanism of cisplatin nephrotoxicity. Alpha-lipoic acid (alpha-LA) has anti-inflammatory effects that inhibit both adhesion molecule expression in human endothelial cells and monocyte adhesion by suppressing the nuclear factor-kappaB (NF-kappaB) signalling pathway. The goals of this study were to investigate the anti-inflammatory effects of alpha-LA during cisplatin-induced renal injury and to examine the mechanisms of protection. METHODS: C57BL/6 mice were given cisplatin (20 mg/kg) with or without alpha-LA treatment (100 mg/kg for 3 days). Renal function, histological changes, adhesion molecule expression and inflammatory cell infiltration were examined. The effect of alpha-LA on NF-kappaB activity was evaluated by examining nuclear translocation and phosphorylation of NF-kappaB p65 subunits in kidney tissue. RESULTS: Cisplatin-induced decreases in renal function, measured by blood urea nitrogen, serum creatinine level and renal tubular injury scores, were attenuated by alpha-LA treatment. alpha-LA decreased the tissue levels of tumour necrosis factor-alpha, the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and suppressed the infiltration of CD11b-positive macrophages. alpha-LA also attenuated the cisplatin-induced increases in the phosphorylation and nuclear translocation of NF- kappaB p65 subunits in kidney tissue. CONCLUSIONS: These results suggest that alpha-LA treatment ameliorates cisplatin-induced acute kidney injury by reducing inflammatory adhesion molecule expression and NF-kappaB activity. PMID- 19474283 TI - Induction of nephrin gene expression by selective cooperation of the retinoic acid receptor and the vitamin D receptor. AB - BACKGROUND: Nephrin is a key molecule involved in the structure and function of the slit diaphragm in the glomerulus. We previously reported that all-trans retinoic acid (ATRA) and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] induced expression of nephrin in murine podocytes. In this report, we investigated roles of the retinoic acid receptor (RAR), the retinoid X receptor (RXR) and the vitamin D receptor (VDR) in the regulation of the nephrin gene. METHODS: Reporter podocytes were treated with agonists and/or antagonists of RAR, RXR or VDR, and activities of the nephrin gene promoter, the retinoic acid response element (RARE) and the vitamin D response element (VDRE) were evaluated. RESULTS: Expression of nephrin in podocytes was up-regulated by ATRA and 1,25(OH)(2)D(3). The nephrin gene promoter was also activated by these agents, which was mediated by RAR and VDR, but unexpectedly, not by RXR. ATRA-triggered, RAR-mediated activation of the nephrin gene promoter was not suppressed by the VDR antagonist. Similarly, ATRA-induced activation of RARE was not inhibited by the VDR antagonist. In contrast, the 1,25(OH)(2)D(3)-triggered, VDR-mediated activation of the nephrin gene promoter was significantly suppressed by the RAR antagonist, but not by RXR antagonists. Interestingly, 1,25(OH)(2)D(3)-induced activation of VDRE was not inhibited by the RAR antagonist. CONCLUSIONS: These results suggested selective cooperation of RAR and VDR in the regulation of the nephrin gene, i.e. (1) ATRA induces nephrin gene expression via RAR independently of RXR and VDR and (2) 1,25(OH)(2)D(3) induces nephrin gene expression via selective cooperation of RAR and VDR, which is independent of RXR. PMID- 19474284 TI - Pre-kidney-transplant blood transfusions do not improve transplantation outcome: a Dutch national study. AB - BACKGROUND: Female renal transplant candidates are prone to be sensitized by prior pregnancies, and undetected historical sensitization might decrease transplantation outcome. Hypothesis of our study was that pre-transplant blood transfusions (PTFs) can elucidate historical sensitization and that the avoidance of the associated antigens can improve transplantation outcome. METHODS: Data from all female non-immunized renal transplant candidates who received a random PTF (rPTF) (n = 620), matched PTF (mPTF) (one HLA-A and B and one HLA-DR match) (n = 86) or donor-specific blood transfusion (DST) (n = 100) between 1996 and 2006 were collected. Complement-dependent cytoxicity was used to detect anti-HLA antibodies. Sensitization and transplantation outcomes after a PTF were analyzed. Non-immunized female renal transplant recipients who did not receive a PTF were used as the control group. RESULTS: In 165 patients, anti-HLA antibodies (IgG) were detected after the PTF. Both historical and primary sensitizations were found. A DST induced donor-specific anti-HLA antibodies in 25% of the DST recipients. Our policy did not improve transplantation outcome in recipients of a kidney from a deceased donor (n = 368) or in recipients of a living donor [DST (n = 49) and mPTF (n = 66)]. CONCLUSIONS: A PTF did elucidate historical sensitization but induce primary sensitization as well. No beneficial effect of PTFs on transplantation outcome was found, and PTFs with the intention to detect historical sensitization are therefore not suggested. PMID- 19474285 TI - Dynorphin immunoreactive fibers contact GnRH neurons in the human hypothalamus. AB - Dynorphin, an endogenous opioid peptide, mediates progesterone-negative feedback on gonadotropin-releasing hormone (GnRH) neurons in other species. The role of dynorphin in humans is unclear. The objective of this study was to determine if dynorphin fibers have close contacts with GnRH neurons in humans. Dual-label immunocytochemistry was performed on postmortem human hypothalamic tissue. The majority of GnRH neurons, 87.5%, had close contacts with dynorphin fibers and multiple close contacts were common, 62.5%. There were no regional differences between the hypothalamus and preoptic area in the distribution of close contacts. More close contacts were identified on the GnRH dendrites compared to the cell bodies (P < .001), but this difference was not significant when corrected for length. In conclusion, dynorphin fibers form close contacts with GnRH neurons in humans. This neuroanatomical evidence may suggest that dynorphin has effects on GnRH regulation in humans as seen in other species. PMID- 19474286 TI - Review: human endogenous retroviruses and the placenta. AB - Up to 8% of the human genome is of retroviral origin. These stably integrated retroviral sequences that characterize the human endogenous retrovirus (HERV) arose from retroviral infections that occurred more than 25 million years ago. The host and the retrovirus have subsequently coevolved as retrovirally derived genetic material is propagated in a Mendelian fashion. Although most HERV sequences are silenced, several have been described that are functional. The effects of some HERV-derived products are linked to human disease; others appear essential to human organ function. The human placenta, unique in its active expression of retroviral sequences that are not expressed in other tissues, may hold the key to an improved understanding of the functional significance of HERVs. In this review, we discuss the contribution of retroelements, particularly HERVs, to placental function and dysfunction. We describe fusogenic and immunosuppressive HERV activities and emphasize epigenetic regulation of retroelement expression. PMID- 19474287 TI - Reviews: adipocytokines in normal and complicated pregnancies. AB - Human pregnancy is characterized by insulin resistance, traditionally attributed to the effects of placental hormones. Normal pregnancy-induced insulin resistance is further enhanced in pregnancy complications, associated with disturbed placental function, such as gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. Compelling evidence suggests that these pregnancy disorders are associated with future development of maternal metabolic syndrome. However, the pathogenetic mechanisms underlying the association between abnormal placental development, insulin resistance, and maternal metabolic syndrome are not fully understood. A large body of evidence has recently supported the role of adipose tissue in the regulation of insulin resistance in both nonpregnant and pregnant participants. In this respect, adipocytokines, which are adipocyte-derived hormones, have been implicated in the regulation of maternal metabolism and gestational insulin resistance. Adipocytokines, including leptin, adiponectin, tumor necrosis factor alpha, interleukin 6, as well as the newly discovered resistin, visfatin, and apelin, are also known to be produced within the intrauterine environment. However, data concerning the pattern of adipocytokines secretion in normal and complicated pregnancies are still limited and partially contradictory. Given the importance of adipose tissue and its hormones in terms of adequate metabolic control and energy homeostasis, we present a review of published data related to the role of adipocytokines in pregnancy, especially in relation to pregnancy complications. Focus will be placed on the functions and other potential roles of the novel adipocytokines resistin, visfatin, and apelin. PMID- 19474288 TI - Intra-amniotic infection upregulates decidual cell vascular endothelial growth factor (VEGF) and neuropilin-1 and -2 expression: implications for infection related preterm birth. AB - Intra-amniotic infection/inflammation (IAI) is a major cause of preterm birth, but the mechanisms responsible are not well understood. This study investigates the effects of IAI on vascular endothelial growth factor (VEGF) as well as VEGF receptor (Flt1, KDR2) and coreceptor (neuropilin-1 and -2) messenger RNA (mRNA) and protein expression at the maternal-fetal interface, both in vitro and in vivo. Decidual stromal cells (DSCs) were isolated from term placentae, purified, and treated with 10(-8) mol/L estradiol (E(2)), 10( -7) mol/L medroxyprogesterone acetate (MPA), both, or vehicle for 7 days. Vascular endothelial growth factor expression in cultured DSCs increased in response to stimulation with interleukin 1 beta (IL-1 beta; 0.01-10 ng/mL)--but not tumor necrosis factor alpha (TNF alpha; 1 ng/mL)--in a concentration-dependent fashion irrespective of the hormonal milieu. This effect appears to be mediated at the level of gene transcription because stimulation with IL-1 beta (but not TNF-alpha) increased expression of VEGF mRNA as measured by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR); a similar increase was seen in neuropilin-1/-2 (but not Flt1 and KDR2) mRNA. Immunohistochemical studies confirmed these observations in vivo. Immunostaining for VEGF and neuropilin-1/-2 (but not Flt1 or KDR2) was increased in serial tissue sections of decidua from women with clinical and histological evidence of IAI versus noninfected controls, and in cultured term DSCs exposed to IL-1 beta. The novel observations that IL-1 beta stimulates VEGF and neuropilin-1/-2 mRNA and protein expression in term DSCs in vitro along with confirmatory in vivo data using immunohistochemistry provide a mechanism by which IAI can alter vascular permeability, thereby facilitating leukocyte trafficking and increasing the risk of abruption, both of which are associated with preterm birth. PMID- 19474289 TI - Expression of angiogenesis-related genes in the cellular component of the blood of preeclamptic women. AB - The purpose of this study is to assess the changes in the expression of angiogenesis-related genes in the cellular component of the blood from preeclamptic patients. Blood samples were obtained from the preeclampsia (PE) and control participants. Cellular RNA was analyzed by reverse transcription polymerase chain reaction (PCR) to identify any angiogenesis-related genes and thereby assess the mRNA expression among women with PE and controls during weeks 35 to 41 of gestation. Significant differences were observed between PE and controls in all of the angiogenesis-related genes examined. In PE, for the increased expression of transforming growth factor-beta1 (TGF-beta1), endoglin and fms-like tyrosine kinase-1 (Flt-1); and the reduced expression of vascular endothelial growth factor (VEGF), placental growth factor (PlGF). fms-Like tyrosine kinase-1 and endoglin significantly correlated with the systolic pressure, while VEGF, Flt-1, and endoglin all correlated with proteinuria. An altered expression of angiogenesis-related genes was demonstrated in the cellular component of blood from preeclamptic patients. These findings indicate that this approach may offer an alternative way for evaluating the pathogenesis of PE. PMID- 19474290 TI - Importance of melastatin-like transient receptor potential 7 and magnesium in the stimulation of osteoblast proliferation and migration by platelet-derived growth factor. AB - Bone is a dynamic tissue that is continuously being remodeled throughout life. Specialized cells called osteoclasts transiently break down old bone (resorption process) at multiple sites as other cells known as osteoblasts are replacing it with new tissue (bone formation). Usually, both resorption and formation processes are in balance and thereby maintain skeletal strength and integrity. This equilibrium is assured by the coordination of proliferation, migration, differentiation, and secretory functions of the osteoblasts, which are essential for adequate formation and resorption processes. Disturbances of this equilibrium may lead to decreased bone mass (osteoporosis), increased bone fragility, and susceptibility to fractures. Epidemiological studies have linked insufficient dietary magnesium (Mg(2+)) intake in humans with low bone mass and osteoporosis. Here, we investigated the roles of Mg(2+) and melastatin-like transient receptor potential 7 (TRPM7), known as Mg(2+) channels, in human osteoblast cell proliferation and migration induced by platelet-derived growth factor (PDGF), which has been involved in the bone remodeling process. PDGF promoted an influx of Mg(2+), enhanced cell migration, and stimulated the gene expression of TRPM7 channels in human osteoblast MG-63 cells. The stimulation of osteoblast proliferation and migration by PDGF was significantly reduced under culture conditions of low extracellular Mg(2+) concentrations. Silencing TRPM7 expression in osteoblasts by specific small interfering RNA prevented the induction by PDGF of Mg(2+) influx, proliferation, and migration. Our results indicate that extracellular Mg(2+) and TRPM7 are important for PDGF-induced proliferation and migration of human osteoblasts. Thus Mg(2+) deficiency, a common condition among the general population, may be associated with altered osteoblast functions leading to inadequate bone formation and the development of osteoporosis. PMID- 19474291 TI - S1P(5) is required for sphingosine 1-phosphate-induced autophagy in human prostate cancer PC-3 cells. AB - Sphingosine 1-phosphate (S1P) is a platelet- and endothelial cell-released lysophospholipid that regulates various cellular functions through activating a specific family of G protein-coupled receptors. Both platelet activation and angiogenesis play important roles in cancer development, implying that cancer cells might encounter a large amount of S1P during these processes. Cancer cells, in the meantime, may experience nutrient deprivation and rely on autophagy for early development. Whether extracellular S1P regulates autophagy remains to be tested. In the present work, we investigated whether autophagy is regulated by S1P in PC-3 cells. Through monitoring the modification patterns of LC3 by Western blotting, we demonstrated that autophagy was induced by exogenously applied S1P in PC-3 cells. This observation was further confirmed by fluorescence microscopy using PC-3 cells stably expressing enhanced green fluorescent protein-LC3. By applying small interfering RNA and dihydro-S1P, S1P(5) activation was found to be involved in this process. Besides, mammalian target of rapamycin signaling was inhibited upon S1P treatment. Taken together, our results suggest that, under serum-starved conditions, S1P further upregulates autophagic activity through S1P(5)-dependent pathways in PC-3 cells. PMID- 19474292 TI - DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading. AB - Discoidin domain receptors (DDRs) 1 and 2, collagen receptors, regulate cell adhesion and a broad range of cell behavior. Their adhesion-dependent regulation of signaling associated with adhesion proteins has not been elucidated. We report a novel mechanism: the cross talk of DDR1 and E-cadherin negatively and adhesion dependently regulated both DDR1 activity and DDR1-suppressed cell spreading. E cadherin forms complexes with both DDR1 isoforms (a and b). E-cadherin regulates DDR1 activity associated with the cell-junction complexes formed between DDR1 and E-cadherin. These complexes are formed independently of DDR1 activation and of beta-catenin and p120-catenin binding to E-cadherin; they are ubiquitous in epithelial cells. Small interfering RNA-mediated gene silencing of E-cadherin restores both DDR1 activity and DDR1-suppressed cell spreading and increases the apically and basally located DDR1 in E-cadherin-null cells. We conclude that E cadherin-mediated adhesions decrease DDR1 activity, which subsequently eliminates DDR1-suppressed cell spreading, by sequestering DDR1 to cell junctions, which prevents its contact with collagen ligand. PMID- 19474293 TI - Protein tyrosine phosphatases PTP-1B and TC-PTP play nonredundant roles in macrophage development and IFN-gamma signaling. AB - The control of tyrosine phosphorylation depends on the fine balance between kinase and phosphatase activities. Protein tyrosine phosphatase 1B (PTP-1B) and T cell protein tyrosine phosphatase (TC-PTP) are 2 closely related phosphatases known to control cytokine signaling. We studied the functional redundancy of PTP 1B and TC-PTP by deleting 1 or both copies of these genes by interbreeding TC-PTP and PTP-1B parental lines. Our results indicate that the double mutant (tcptp(-/ )ptp1b(-/-)) is lethal at day E9.5-10.5 of embryonic development with constitutive phosphorylation of Stat1. Mice heterozygous for TC-PTP on a PTP-1B deficient background (tcptp(+/-)ptp1b(-/-)) developed signs of inflammation. Macrophages from these animals were highly sensitive to IFN-gamma, as demonstrated by increased Stat1 phosphorylation and nitric oxide production. In addition, splenic T cells demonstrated increased IFN-gamma secretion capacity. Mice with deletions of single copies of TC-PTP and PTP-1B (tcptp(+/-)ptp1b(+/-)) exhibited normal development, confirming that these genes are not interchangeable. Together, these data indicate a nonredundant role for PTP-1B and TC-PTP in the regulation of IFN signaling. PMID- 19474294 TI - Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. AB - We have developed an online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs). Reported TASs were common [median risk allele frequency 36%, interquartile range (IQR) 21%-53%] and were associated with modest effect sizes [median odds ratio (OR) 1.33, IQR 1.20-1.61]. Among 20 genomic annotation sets, reported TASs were significantly overrepresented only in nonsynonymous sites [OR = 3.9 (2.2-7.0), p = 3.5 x 10(-7)] and 5kb-promoter regions [OR = 2.3 (1.5-3.6), p = 3 x 10(-4)] compared to SNPs randomly selected from genotyping arrays. Although 88% of TASs were intronic (45%) or intergenic (43%), TASs were not overrepresented in introns and were significantly depleted in intergenic regions [OR = 0.44 (0.34-0.58), p = 2.0 x 10(-9)]. Only slightly more TASs than expected by chance were predicted to be in regions under positive selection [OR = 1.3 (0.8-2.1), p = 0.2]. This new online resource, together with bioinformatic predictions of the underlying functionality at trait/disease associated loci, is well-suited to guide future investigations of the role of common variants in complex disease etiology. PMID- 19474295 TI - Neural deficits contribute to respiratory insufficiency in Pompe disease. AB - Pompe disease is a severe form of muscular dystrophy due to glycogen accumulation in all tissues, especially striated muscle. Disease severity is directly related to the deficiency of acid alpha-glucosidase (GAA), which degrades glycogen in the lysosome. Respiratory dysfunction is a hallmark of the disease, muscle weakness has been viewed as the underlying cause, and the possibility of an associated neural contribution has not been evaluated previously. Therefore, we examined behavioral and neurophysiological aspects of breathing in 2 animal models of Pompe disease--the Gaa(-/-) mouse and a transgenic line (MTP) expressing GAA only in skeletal muscle, as well as a detailed analysis of the CNS in a Pompe disease patient. Glycogen content was elevated in the Gaa(-/-) mouse cervical spinal cord. Retrograde labeling of phrenic motoneurons showed significantly greater soma size in Gaa(-/-) mice vs. isogenic controls, and glycogen was observed in Gaa(-/-) phrenic motoneurons. Ventilation, assessed via plethysmography, was attenuated during quiet breathing and hypercapnic challenge in Gaa(-/-) mice (6 to >21 months of age) vs. controls. We confirmed that MTP mice had normal diaphragmatic contractile properties; however, MTP mice had ventilation similar to the Gaa(-/-) mice during quiet breathing. Neurophysiological recordings indicated that efferent phrenic nerve inspiratory burst amplitudes were substantially lower in Gaa(-/-) and MTP mice vs. controls. In human samples, we demonstrated similar pathology in the cervical spinal cord and greater accumulation of glycogen in spinal cord compared with brain. We conclude that neural output to the diaphragm is deficient in Gaa(-/-) mice, and therapies targeting muscle alone may be ineffective in Pompe disease. PMID- 19474296 TI - Profile of John Michael David Coey. PMID- 19474297 TI - Functional genomic analysis of amniotic fluid cell-free mRNA suggests that oxidative stress is significant in Down syndrome fetuses. AB - To characterize the differences between second trimester Down syndrome (DS) and euploid fetuses, we used Affymetrix microarrays to compare gene expression in uncultured amniotic fluid supernatant samples. Functional pathway analysis highlighted the importance of oxidative stress, ion transport, and G protein signaling in the DS fetuses. Further evidence supporting these results was derived by correlating the observed gene expression patterns to those of small molecule drugs via the Connectivity Map. Our results suggest that there are secondary adverse consequences of DS evident in the second trimester, leading to testable hypotheses about possible antenatal therapy for DS. PMID- 19474298 TI - Functional and shunt states of bacteriorhodopsin resolved by 250 GHz dynamic nuclear polarization-enhanced solid-state NMR. AB - Observation and structural studies of reaction intermediates of proteins are challenging because of the mixtures of states usually present at low concentrations. Here, we use a 250 GHz gyrotron (cyclotron resonance maser) and cryogenic temperatures to perform high-frequency dynamic nuclear polarization (DNP) NMR experiments that enhance sensitivity in magic-angle spinning NMR spectra of cryo-trapped photocycle intermediates of bacteriorhodopsin (bR) by a factor of approximately 90. Multidimensional spectroscopy of U-(13)C,(15)N labeled samples resolved coexisting states and allowed chemical shift assignments in the retinylidene chromophore for several intermediates not observed previously. The correlation spectra reveal unexpected heterogeneity in dark adapted bR, distortion in the K state, and, most importantly, 4 discrete L substates. Thermal relaxation of the mixture of L's showed that 3 of these substates revert to bR(568) and that only the 1 substate with both the strongest counterion and a fully relaxed 13-cis bond is functional. These definitive observations of functional and shunt states in the bR photocycle provide a preview of the mechanistic insights that will be accessible in membrane proteins via sensitivity-enhanced DNP NMR. These observations would have not been possible absent the signal enhancement available from DNP. PMID- 19474299 TI - Brain-size evolution and sociality in Carnivora. AB - Increased encephalization, or larger brain volume relative to body mass, is a repeated theme in vertebrate evolution. Here we present an extensive sampling of relative brain sizes in fossil and extant taxa in the mammalian order Carnivora (cats, dogs, bears, weasels, and their relatives). By using Akaike Information Criterion model selection and endocranial volume and body mass data for 289 species (including 125 fossil taxa), we document clade-specific evolutionary transformations in encephalization allometries. These evolutionary transformations include multiple independent encephalization increases and decreases in addition to a remarkably static basal Carnivora allometry that characterizes much of the suborder Feliformia and some taxa in the suborder Caniformia across much of their evolutionary history, emphasizing that complex processes shaped the modern distribution of encephalization across Carnivora. This analysis also permits critical evaluation of the social brain hypothesis (SBH), which predicts a close association between sociality and increased encephalization. Previous analyses based on living species alone appeared to support the SBH with respect to Carnivora, but those results are entirely dependent on data from modern Canidae (dogs). Incorporation of fossil data further reveals that no association exists between sociality and encephalization across Carnivora and that support for sociality as a causal agent of encephalization increase disappears for this clade. PMID- 19474300 TI - Genetic evidence for shared mechanisms of epimorphic regeneration in zebrafish. AB - In a microarray-based gene profiling analysis of Muller glia-derived retinal stem cells in light-damaged retinas from adult zebrafish, we found that 2 genes required for regeneration of fin and heart tissues in zebrafish, hspd1 (heat shock 60-kDa protein 1) and mps1 (monopolar spindle 1), were up-regulated. Expression of both genes in the neurogenic Muller glia and progenitors was independently verified by quantitative reverse transcriptase PCR and in situ hybridization. Functional analysis of temperature-sensitive mutants of hspd1 and mps1 revealed that both are necessary for Muller glia-based cone photoreceptor regeneration in adult zebrafish retina. In the amputated fin, hspd1 is required for the induction of mesenchymal stem cells and blastema formation, whereas mps1 is required at a later step for rapid cell proliferation and outgrowth. This temporal sequence of hspd1 and mps1 function is conserved in the regenerating retina. Comparison of gene expression profiles from regenerating zebrafish retina, caudal fin, and heart muscle revealed additional candidate genes potentially implicated in injury-induced epimorphic regeneration in diverse zebrafish tissues. PMID- 19474302 TI - Chemically inducible inactivation of protein synthesis in genetically targeted neurons. PMID- 19474303 TI - The delta2 glutamate-like receptor undergoes similar conformational changes as other ionotropic glutamate receptors. PMID- 19474304 TI - Selectivity for conspecific vocalizations within the primate insular cortex. PMID- 19474305 TI - Human APOE isoform-dependent effects on brain beta-amyloid levels in PDAPP transgenic mice. AB - To investigate the role of human apolipoprotein E (apoE) on Abeta deposition in vivo, we crossed PDAPP mice lacking mouse Apoe to targeted replacement mice expressing human apoE (PDAPP/TRE2, PDAPP/TRE3, or PDAPP/TRE4). We then measured the levels of apoE protein and Abeta peptides in plasma, CSF, and brain homogenates in these mice at different ages. We also quantified the amount of brain Abeta and amyloid burden in 18-month-old mice. In young PDAPP/TRE4 mice that were analyzed at an age before brain Abeta deposition, we observed a significant decrease in the levels of apoE in CSF and brain when compared with age-matched mice expressing either human E2 or E3. The brain levels of Abeta42 in PDAPP/TRE4 mice were substantially elevated even at this very early time point. In older PDAPP/TRE4 mice, the levels of insoluble apoE protein increased in parallel to the dramatic rise in brain Abeta burden, and the majority of apoE was associated with Abeta. In TRE4 only mice, we also observed a significant decrease in the level of apoE in brain homogenates. Since the relative level of apoE mRNA was equivalent in PDAPP/TRE and TRE only mice, it appears that post-translational mechanisms influence the levels of apoE protein in brain (E4 < E3 << E2), resulting in early and dramatic apoE isoform-dependent effects on brain Abeta levels (E4 >> E3 > E2) that increase with age. Therapeutic strategies aimed at increasing the soluble levels of apoE protein, regardless of isoform, may effectively prevent and (or) treat Alzheimer's disease. PMID- 19474306 TI - Functional role of a specialized class of spinal commissural inhibitory neurons during fast escapes in zebrafish. AB - In teleost fish, the Mauthner (M) cell, a large reticulospinal neuron in the brainstem, triggers escape behavior. Spinal commissural inhibitory interneurons that are electrotonically excited by the M-axon have been identified, but the behavioral roles of these neurons have not yet been addressed. Here, we studied these neurons, named CoLo (commissural local), in larval zebrafish using an enhancer-trap line in which the entire population of CoLos was visualized by green fluorescent protein. CoLos were present at one cell per hemi-segment. Electrophysiological recordings showed that an M-spike evoked a spike in CoLos via electrotonic transmission and that CoLos made monosynaptic inhibitory connections onto contralateral primary motoneurons, consistent with the results in adult goldfish. We further showed that CoLos were active only during escapes. We examined the behavioral roles of CoLos by investigating escape behaviors in CoLo-ablated larvae. The results showed that the escape behaviors evoked by sound/vibration stimuli were often impaired with a reduced initial bend of the body, indicating that CoLos play important roles in initiating escapes. We obtained several lines of evidence that strongly suggested that the impaired escapes occurred during bilateral activation of the M-cells: in normal larvae, CoLo-mediated inhibitory circuits enable animals to perform escapes even in these occasions by silencing the output of the slightly delayed firing of the second M cell. This study illustrates (1) a clear example of the behavioral role of a specialized class of interneurons and (2) the capacity of the spinal circuits to filter descending commands and thereby produce the appropriate behavior. PMID- 19474308 TI - TMEM16B, a novel protein with calcium-dependent chloride channel activity, associates with a presynaptic protein complex in photoreceptor terminals. AB - Photoreceptor ribbon synapses release glutamate in response to graded changes in membrane potential evoked by vast, logarithmically scalable light intensities. Neurotransmitter release is modulated by intracellular calcium levels. Large Ca(2+)-dependent chloride currents are important regulators of synaptic transmission from photoreceptors to second-order neurons; the molecular basis underlying these currents is unclear. We cloned human and mouse TMEM16B, a member of the TMEM16 family of transmembrane proteins, and show that it is abundantly present in the photoreceptor synaptic terminals in mouse retina. TMEM16B colocalizes with adaptor proteins PSD95, VELI3, and MPP4 at the ribbon synapses and contains a consensus PDZ class I binding motif capable of interacting with PDZ domains of PSD95. Furthermore, TMEM16B is lost from photoreceptor membranes of MPP4-deficient mice. This suggests that TMEM16B is a novel component of a presynaptic protein complex recruited to specialized plasma membrane domains of photoreceptors. TMEM16B confers Ca(2+)-dependent chloride currents when overexpressed in mammalian cells as measured by halide sensitive fluorescent protein assays and whole-cell patch-clamp recordings. The compartmentalized localization and the electrophysiological properties suggest TMEM16B to be a strong candidate for the long sought-after Ca(2+)-dependent chloride channel in the photoreceptor synapse. PMID- 19474307 TI - Visualization of dopamine transporter trafficking in live neurons by use of fluorescent cocaine analogs. AB - The dopamine transporter (DAT) mediates reuptake of dopamine from the synaptic cleft and is a target for widely abused psychostimulants such as cocaine and amphetamine. Nonetheless, little is known about the cellular distribution and trafficking of natively expressed DAT. Here we use novel fluorescently tagged cocaine analogs to visualize DAT and DAT trafficking in cultured live midbrain dopaminergic neurons. The fluorescent tags were extended from the tropane N position of 2beta-carbomethoxy-3beta-(3,4-dichlorophenyl)tropane using an ethylamino-linker. The rhodamine-, OR Green-, or Cy3-labeled ligands had high binding affinity for DAT and enabled specific labeling of DAT in live neurons and visualization by confocal imaging. In the dopaminergic neurons, DAT was uniformly distributed in the plasma membrane of the soma, the neuronal extensions, and varicosities along these extensions. FRAP (fluorescence recovery after photobleaching) experiments demonstrated bidirectional movement of DAT in the extensions and indicated that DAT is highly mobile both in the extensions and in the varicosities (immobile fraction less than approximately 30%). DAT was constitutively internalized into vesicular structures likely representing intracellular transporter pools. The internalization was blocked by lentiviral mediated expression of dominant-negative dynamin and internalized DAT displayed partial colocalization with the early endosomal marker EGFP-Rab5 and with the transferrin receptor. DAT internalization and function was not affected by activation of protein kinase C (PKC) with phorbol-12-myristate-13-acetate (PMA) or by inhibition with staurosporine or GF109203X. These data are in contrast to findings for DAT in transfected heterologous cells and challenge the paradigm that trafficking and cellular distribution of endogenous DAT is subject to regulation by PKC. PMID- 19474309 TI - Pregnanolone sulfate promotes desensitization of activated NMDA receptors. AB - Neurosteroids are potent neuromodulators which act in part by binding to and modifying the activity of neurotransmitter-gated channels. Pregnanolone sulfate (PAS) is an endogenous neurosteroid that inhibits NMDA receptors and is neuroprotective in vivo. To delineate the mechanism of NMDA receptor inhibition by pregnanolone sulfate we used kinetic analyses of equilibrium single-channel currents recorded from individual GluN1/GluN2A receptors. Results show that PAS (0.1 mM) reduces single-channel open probability by 50% solely by increasing approximately 5-fold the mean time spent by receptors in closed conformations. From these data we derive a kinetic scheme that summarizes the effects of PAS on single channel kinetics, accounts for the PAS effects on macroscopic responses and leads us to propose that PAS inhibits NMDA receptor activity by shifting active receptors into desensitized conformations. These findings highlight the neurosteroid inhibitory site on NMDA receptors as a valuable therapeutic target against excitotoxic pathologies including acute and chronic neurodegeneration. PMID- 19474310 TI - Dopamine depletion induces distinct compensatory gene expression changes in DARPP 32 signal transduction cascades of striatonigral and striatopallidal neurons. AB - Functional alterations in striatal projection neurons play a critical role in the development of motor symptoms in Parkinson's disease (PD), but their molecular adaptation to dopamine depletion remains poorly understood. In particular, type and extent of regulation in postsynaptic signal transduction pathways that determine the responsiveness of striatal projection neurons to incoming stimuli, are currently unknown. Using cell-type-specific transcriptome analyses in a rodent model of chronic dopamine depletion, we identified large-scale gene expression changes, including neurotransmitter receptors, signal transduction cascades, and target proteins of dopamine signaling in striatonigral and striatopallidal neurons. Within the dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32) cascade of enzymes that plays a central role in signal integration of dopaminoceptive neurons multiple catalytic and regulatory subunits change their mRNA expression levels. In addition to the number of genes the fact that the alterations occur at multiple levels stresses the biological relevance of transcriptional regulation for adaptations of postsynaptic signaling pathways. The overall pattern of changes in both striatonigral and striatopallidal neurons is compatible with homeostatic mechanisms. In accordance with the distinct biological effects of dopamine D(1) and D(2) receptor stimulation, the alterations of the transcriptional profiles most likely result in prodopaminergic phosphorylation patterns. Our data provide insight into the disease-related plasticity of functional genomic networks in vivo that might contribute to the protracted preclinical phase of PD. In addition, the data have potential implications for the symptomatic treatment of the disease. PMID- 19474311 TI - Hippocampal place cell firing patterns can induce long-term synaptic plasticity in vitro. AB - In the hippocampus, synaptic strength between pyramidal cells is modifiable by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD), both of which require coincident presynaptic and postsynaptic activity. In vivo, many pyramidal cells exhibit location-specific activity patterns and are known as "place cells." The combination of these factors suggests that synaptic plasticity will be induced at synapses connecting place cells with overlapping firing fields, because such cells fire coincidentally when the rat is in a specific part of the environment. However, this prediction, which is important for models of how long-term synaptic plasticity can be used to encode space in the hippocampal network, has not been tested. To investigate this, action potential time series recorded simultaneously from place cells in freely moving rats were replayed concurrently into postsynaptic CA1 pyramidal cells and presynaptic inputs during perforated patch-clamp recordings from adult hippocampal slices. Place cell firing patterns induced large, pathway-specific, NMDAR-dependent LTP that was rapidly expressed within a few minutes. However, place-cell LTP was induced only if the two place cells had overlapping firing fields and if the cholinergic tone present in the hippocampus during exploration was restored by bath application of the cholinergic agonist carbachol. LTD was never observed in response to place cell firing patterns. Our findings demonstrate that spike patterns from hippocampal place cells can robustly induce NMDAR-dependent LTP, providing important evidence in support of a model in which spatial distance is encoded as the strength of synaptic connections between place cells. PMID- 19474312 TI - Stability of thalamocortical synaptic transmission across awake brain states. AB - Sensory cortical neurons are highly sensitive to brain state, with many neurons showing changes in spatial and/or temporal response properties and some neurons becoming virtually unresponsive when subjects are not alert. Although some of these changes are undoubtedly attributable to state-related filtering at the thalamic level, another likely source of such effects is the thalamocortical (TC) synapse, where activation of nicotinic receptors on TC terminals have been shown to enhance synaptic transmission in vitro. However, monosynaptic TC synaptic transmission has not been directly examined during different states of alertness. Here, in awake rabbits that shifted between alert and non-alert EEG states, we examined the monosynaptic TC responses and short-term synaptic dynamics generated by spontaneous impulses of single visual and somatosensory TC neurons. We did this using spike-triggered current source-density analysis, an approach that enables assessment of monosynaptic extracellular currents generated in different cortical layers by impulses of single TC afferents. Spontaneous firing rates of TC neurons were higher, and burst rates were much lower in the alert state. However, we found no state-related changes in the amplitude of monosynaptic TC responses when TC spikes with similar preceding interspike interval were compared. Moreover, the relationship between the preceding interspike interval of the TC spike and postsynaptic response amplitude was not influenced by state. These data indicate that TC synaptic transmission and dynamics are highly conserved across different states of alertness and that observed state-related changes in receptive field properties that occur at the cortical level result from other mechanisms. PMID- 19474313 TI - Akt signals through the mammalian target of rapamycin pathway to regulate CNS myelination. AB - Mammalian target of rapamycin (mTOR), a well known Akt substrate, regulates multiple cellular functions including cell growth and protein synthesis. The current study identifies a novel role of the Akt/mTOR pathway as a regulator of CNS myelination. Previously, we showed that overexpressing constitutively active Akt in oligodendrocytes in a transgenic mouse model induces enhanced CNS myelination, with no changes in the proliferation or survival of oligodendrocyte progenitor or mature cells. The present study focused on the signaling mechanisms regulating this hypermyelination induced by Akt. Activation of mTOR and its downstream substrates (p70S6 kinase and S6 ribosomal protein) was observed in Akt overexpressing oligodendrocytes. When mTOR signaling was inhibited chronically in vivo with rapamycin starting at 6 weeks of age, the observed hypermyelination was reduced to approximately the amount of myelin seen in wild-type mice. mTOR inhibition had little impact on wild-type myelination between 6 and 12 weeks of age, suggesting that, in normal adults, myelination is relatively complete and is no longer regulated by mTOR signaling. However, when mTOR was chronically inhibited in young adult wild-type mice, myelination was reduced. These results suggest that, during active myelination, the major Akt signal regulating CNS myelination is the mTOR pathway. PMID- 19474314 TI - Effects of restricted basilar papillar lesions and hair cell regeneration on auditory forebrain frequency organization in adult European starlings. AB - The frequency organization of neurons in the forebrain Field L complex (FLC) of adult starlings was investigated to determine the effects of hair cell (HC) destruction in the basal portion of the basilar papilla (BP) and of subsequent HC regeneration. Conventional microelectrode mapping techniques were used in normal starlings and in lesioned starlings either 2 d or 6-10 weeks after aminoglycoside treatment. Histological examination of the BP and recordings of auditory brainstem evoked responses confirmed massive loss of HCs in the basal portion of the BP and hearing losses at frequencies >2 kHz in starlings tested 2 d after aminoglycoside treatment. In these birds, all neurons in the region of the FLC in which characteristic frequencies (CFs) normally increase from 2 to 6 kHz had CF in the range of 2-4 kHz. The significantly elevated thresholds of responses in this region of altered tonotopic organization indicated that they were the residue of prelesion responses and did not reflect CNS plasticity. In the long term recovery birds, there was histological evidence of substantial HC regeneration. The tonotopic organization of the high-frequency region of the FLC did not differ from that in normal starlings, but the mean threshold at CF in this frequency range was intermediate between the values in the normal and lesioned short-recovery groups. The recovery of normal tonotopicity indicates considerable stability of the topography of neuronal connections in the avian auditory system, but the residual loss of sensitivity suggests deficiencies in high-frequency HC function. PMID- 19474316 TI - Membrane potential changes in dendritic spines during action potentials and synaptic input. AB - Excitatory input onto many neurons in the brain occurs onto specialized projections called dendritic spines. Despite their potential importance in neuronal function, direct experimental evidence on electrical signaling in dendritic spines is lacking as their small size makes them inaccessible to standard electrophysiological techniques. Here, we investigate electrical signaling in dendritic spines using voltage-sensitive dye imaging in cortical pyramidal neurons during backpropagating action potentials and synaptic input. Backpropagating action potentials were found to fully invade dendritic spines without voltage loss. The voltage change in dendritic spines during synaptic input ranged from a few millivolts up to approximately 20 mV. During hyperpolarization of the membrane potential, the amplitude of the synaptic voltage in spines was increased, consistent with the expected change resulting from the increased driving force. This observation suggests that voltage activated channels do not significantly boost the voltage response in dendritic spines during synaptic input. Finally, we used simulations of our experimental observations in morphologically realistic models to estimate spine neck resistance. These simulations indicated that spine neck resistance ranges up to approximately 500 Mohms. Spine neck resistances of this magnitude reduce somatic EPSPs by <15%, indicating that the spine neck is unlikely to act as a physical device to significantly modify synaptic strength. PMID- 19474315 TI - UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors. AB - Adaptor proteins are likely to modulate spatially and temporally the trafficking of a number of membrane proteins, including neuronal nicotinic acetylcholine receptors (nAChRs). A yeast two-hybrid screen identified a novel UBX-containing protein, UBXD4, as one of the cytosolic proteins that interact directly with the alpha3 and alpha4 nAChR subunits. The function of UBX-containing proteins is largely unknown. Immunoprecipitation and confocal microscopy confirmed the interaction of UBXD4 with alpha3-containing nAChRs (alpha3* nAChRs) expressed in HEK293 cells, PC12 cells, and rat cortical neurons. Overexpression of UBXD4 in differentiated PC12 cells (dPC12) increased nAChR cell surface expression, especially that of the alpha3beta2 subtype. These findings were corroborated by electrophysiology, immunofluorescent staining, and biotinylation of surface receptors. Silencing of UBXD4 led to a significant reduction of alpha3* nAChRs in rat cortical neurons and dPC12 cells. Biochemical and immunofluorescence studies of endogenous UBXD4 showed that the protein is located in both the ER and cis Golgi compartments. Our investigations also showed that the alpha3 subunit is ubiquitinated and that UBXD4 can interfere with its ubiquitination and consequent degradation by the proteasome. Our data suggest that UBXD4 modulates the distribution of alpha3* nAChRs between specialized intracellular compartments and the plasma membrane. This effect is achieved by controlling the stability of the alpha3 subunit and, consequently, the number of receptors at the cell surface. PMID- 19474317 TI - Lineage and birth date specify motor neuron targeting and dendritic architecture in adult Drosophila. AB - Locomotion in adult Drosophila depends on motor neurons that target a set of multifibered muscles in the appendages. Here, we describe the development of motor neurons in adult Drosophila, focusing on those that target the legs. Leg motor neurons are born from at least 11 neuroblast lineages, but two lineages generate the majority of these cells. Using genetic single-cell labeling methods, we analyze the birth order, muscle targeting, and dendritic arbors for most of the leg motor neurons. Our results reveal that each leg motor neuron is born at a characteristic time of development, from a specific lineage, and has a stereotyped dendritic architecture. Motor axons that target a particular leg segment or muscle have similar dendritic arbors but can derive from different lineages. Thus, although Drosophila uses a lineage-based method to generate leg motor neurons, individual lineages are not dedicated to generate neurons that target a single leg segment or muscle type. PMID- 19474319 TI - Short-latency influence of medial frontal cortex on primary motor cortex during action selection under conflict. AB - Medial frontal cortex (MFC) is crucial when actions have to be inhibited, reprogrammed, or selected under conflict, but the precise mechanism by which it operates is unclear. Importantly, how and when the MFC influences the primary motor cortex (M1) during action selection is unknown. Using paired-pulse transcranial magnetic stimulation, we investigated functional connectivity between the presupplementary motor area (pre-SMA) part of MFC and M1. We found that functional connectivity increased in a manner dependent on cognitive context: pre-SMA facilitated the motor evoked-potential elicited by M1 stimulation only during action reprogramming, but not when otherwise identical actions were made in the absence of conflict. The effect was anatomically specific to pre-SMA; it was not seen when adjacent brain regions were stimulated. We discuss implications for the anatomical pathways mediating the observed effects. PMID- 19474318 TI - Cortical lesion-induced visual hemineglect is prevented by NMDA antagonist pretreatment. AB - Large unilateral visual cortex lesions produce enduring contralesional visual orientation deficits. To examine whether glutamate excitotoxicity is involved in establishing these deficits, cats were pretreated with the NMDA receptor antagonist dizocilpine (MK-801) 30 min before unilateral visual cortex ablation. Pretreated MK-801 animals were trained first in an orientation task in which they were required to fixate directly ahead and then orient to stimuli introduced at various eccentricities throughout the visual field. They did not display the characteristic ipsilesional head and neck asymmetries and/or spontaneous ipsiversive rotational behaviors or show the profound contralesional visual neglect seen postoperatively in nonpretreated control animals. Rather, pretreated animals were able to orient to visual stimuli in the contralesional hemifield immediately following surgical recovery. Postmortem histology revealed severe retrograde degeneration of the ipsilesional lateral geniculate nucleus in both experimental groups, suggesting that postlesion visuomotor behavioral competencies in pretreated animals are attributable to preserved function in nongeniculocortical visual pathways. These observations are consistent with the hypothesis that visual cortex lesions normally induce secondary alterations via NMDA-mediated excitotoxicity in these other pathways that prevents them from supporting visuomotor behaviors. The similar behavioral competencies of MK-801 pretreated animals and those whose lesion-induced deficits are ameliorated by removing basal ganglia afferents to the ipsilesional superior colliculus are consistent with this hypothesis and highlight the normal functional capabilities of this circuit. It is likely that MK-801 pretreatment acts, at least in part, by preserving the normal interhemispheric control dynamics with which the basal ganglia influence superior colliculus-mediated orientation behaviors. PMID- 19474320 TI - Distinct effects of Hedgehog signaling on neuronal fate specification and cell cycle progression in the embryonic mouse retina. AB - Cell-extrinsic signals can profoundly influence the production of various neurons from common progenitors. Yet mechanisms by which extrinsic signals coordinate progenitor cell proliferation, cell cycle exit, and cell fate choices are not well understood. Here, we address whether Hedgehog (Hh) signals independently regulate progenitor proliferation and neuronal fate decisions in the embryonic mouse retina. Conditional ablation of the essential Hh signaling component Smoothened (Smo) in proliferating progenitors, rather than in nascent postmitotic neurons, leads to a dramatic increase of retinal ganglion cells (RGCs) and a mild increase of cone photoreceptor precursors without significantly affecting other early-born neuronal cell types. In addition, Smo-deficient progenitors exhibit aberrant expression of cell cycle regulators and delayed G(1)/S transition, especially during the late embryonic stages, resulting in a reduced progenitor pool by birth. Deficiency in Smo function also causes reduced expression of the basic helix-loop-helix transcription repressor Hes1 and preferential elevation of the proneural gene Math5. In Smo and Math5 double knock-out mutants, the enhanced RGC production observed in Smo-deficient retinas is abolished, whereas defects in the G(1)/S transition persist, suggesting that Math5 mediates the Hh effect on neuronal fate specification but not on cell proliferation. These findings demonstrate that Hh signals regulate progenitor pool expansion primarily by promoting cell cycle progression and influence cell cycle exit and neuronal fates by controlling specific proneural genes. Together, these distinct cellular effects of Hh signaling in neural progenitor cells coordinate a balanced production of diverse neuronal cell types. PMID- 19474322 TI - Prolonged withdrawal from repeated noncontingent cocaine exposure increases NMDA receptor expression and ERK activity in the nucleus accumbens. AB - Cocaine-induced changes in glutamatergic synaptic transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play a key role in cocaine behavioral effects. Activation of ionotropic glutamate receptor NMDA receptor (NMDAR) in the VTA is critical for the development of cocaine psychomotor sensitization. However, the role of NMDAR in the NAc, a brain area critical for the expression of cocaine psychomotor sensitization, remains to be explored. Here, we show that repeated noncontingent cocaine injections increased NAc NMDAR subunits, NR1, NR2A, and NR2B 21 d, but not 1 d, after withdrawal from cocaine. These changes were associated with an increase in the GluR1 subunit of the AMPA receptor. We also found a time-dependent increase in extracellular signal regulated kinase (ERK) activity which correlated with the increased expression of NMDAR subunits. Furthermore, the increase in GluR1 and ERK activity was blocked after inhibition of NR2B-containing NMDAR during the development of cocaine psychomotor sensitization or when the MEK (mitogen-activated protein/ERK kinase) inhibitor was microinjected into the NAc 21 d after withdrawal from cocaine. Together, these results suggest that the development of cocaine psychomotor sensitization triggers a delayed increase in the expression of NMDAR subunits in the NAc, which in turn enhances the activity of ERK. Enhanced ERK activity drives the increased expression of the GluR1 subunits, which increases the excitability of NAc neurons after prolonged withdrawal from cocaine and results in enduring expression of psychomotor sensitization. PMID- 19474321 TI - The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. AB - Understanding of the sequence and nature of the events that govern neuron microglia communication is critical for the discovery of new mechanisms and targets for chronic pain treatment. The neuronal chemokine fractalkine (FKN) and its microglial receptor CX3CR1 may mediate such a function in the dorsal horn of the spinal cord after cleavage of the extracellular domain of this transmembrane chemokine by a protease. Here we report that in neuropathic rat dorsal horn, with dorsal root-attached preparations, soluble FKN (sFKN) contents are increased in the superfusates collected after noxious-like electrical stimulation of ipsilateral primary afferent fibers. The increase of sFKN is prevented by morpholinurea-leucine-homophenylalanine-vinyl sulfone-phenyl (LHVS), an irreversible inhibitor of cathepsin S (CatS) whose proteolytic activity is also increased in the superfusates. The source of CatS activity is microglial cells activated by the peripheral nerve injury and secreting the enzyme, as a result of primary afferent fiber stimulation. Indeed, the acute activation of dorsal horn microglia by lipopolysaccharide results in increased CatS activity in the superfusates, followed by increased sFKN contents. Consistent with these observations ex vivo, the levels of both sFKN and CatS activity in CSF samples increased significantly after peripheral nerve injury, associated with spinal microglial activation. Finally, because we found that both FKN immunoreactivity and mRNA are confined to dorsal horn neurons, we suggest that under neuropathic conditions, noxious stimulation of primary afferent fibers induces release of CatS from microglia, which liberates FKN from dorsal horn neurons, thereby contributing to the amplification and maintenance of chronic pain. PMID- 19474323 TI - The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. AB - Understanding molecular mechanisms mediating epileptogenesis is critical for developing more effective therapies for epilepsy. We recently found that the mammalian target of rapamycin (mTOR) signaling pathway is involved in epileptogenesis, and mTOR inhibitors prevent epilepsy in a mouse model of tuberous sclerosis complex. Here, we investigated the potential role of mTOR in a rat model of temporal lobe epilepsy initiated by status epilepticus. Acute kainate-induced seizures resulted in biphasic activation of the mTOR pathway, as evident by an increase in phospho-S6 (P-S6) expression. An initial rise in P-S6 expression started approximately 1 h after seizure onset, peaked at 3-6 h, and returned to baseline by 24 h in both hippocampus and neocortex, reflecting widespread stimulation of mTOR signaling by acute seizure activity. After resolution of status epilepticus, a second increase in P-S6 was observed in hippocampus only, which started at 3 d, peaked 5-10 d, and persisted for several weeks after kainate injection, correlating with the development of chronic epileptogenesis within hippocampus. The mTOR inhibitor rapamycin, administered before kainate, blocked both the acute and chronic phases of seizure-induced mTOR activation and decreased kainate-induced neuronal cell death, neurogenesis, mossy fiber sprouting, and the development of spontaneous epilepsy. Late rapamycin treatment, after termination of status epilepticus, blocked the chronic phase of mTOR activation and reduced mossy fiber sprouting and epilepsy but not neurogenesis or neuronal death. These findings indicate that mTOR signaling mediates mechanisms of epileptogenesis in the kainate rat model and that mTOR inhibitors have potential antiepileptogenic effects in this model. PMID- 19474324 TI - Hindbrain cocaine- and amphetamine-regulated transcript induces hypothermia mediated by GLP-1 receptors. AB - Cocaine- and amphetamine-regulated transcript (CART) peptides are widely distributed throughout the neuraxis, including regions associated with energy balance. CART's classification as a catabolic neuropeptide is based on its inhibitory effects on feeding, coexpression with arcuate nucleus proopiomelanocortin neurons, and on limited analysis of its energy expenditure effects. Here, we investigate whether (1) caudal brainstem delivery of CART produces energetic, cardiovascular, and glycemic effects, (2) forebrain-caudal brainstem neural communication is required for those effects, and (3) glucagon like peptide-1 receptors (GLP-1Rs) contribute to the mediation of CART-induced effects. Core temperature (Tc), heart rate (HR), activity, and blood glucose were measured in rats injected fourth intracerebroventricularly with CART (0.1, 1.0, and 2.0 microg). Food was withheld during physiologic recording and returned for overnight measurement of intake and body weight. CART induced a long-lasting (>6 h) hypothermia: a 1.5 degrees C and 1.6 degrees C drop in Tc for the 1.0 and 2.0 microg doses. Hindbrain CART application reduced food intake and body weight and increased blood glucose levels; no change in HR or activity was observed. Supracollicular decerebration eliminated the hypothermic response observed in intact rats to hindbrain ventricular CART, suggesting that forebrain processing is required for hypothermia. Pretreatment with the GLP-1R antagonist (exendin-9 39) in control rats attenuated CART hypothermia and hypophagia, indicating that GLP-1R activation contributes to hypothermic and hypophagic effects of hindbrain CART, whereas CART-induced hyperglycemia was not altered by GLP-1R blockade. Data reveal a novel function of CART in temperature regulation and open possibilities for future studies on the clinical potential of the hypothermic effect. PMID- 19474325 TI - Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus. AB - Depolarizing and excitatory GABA actions are thought to be important in cortical development. We show here that GABA has no excitatory action on CA3 pyramidal neurons in hippocampal slices from neonatal NKCC1(-/-) mice that lack the Na-K 2Cl cotransporter isoform 1. Strikingly, NKCC1(-/-) slices generated endogenous network events similar to giant depolarizing potentials (GDPs), but, unlike in wild-type slices, the GDPs were not facilitated by the GABA(A) agonist isoguvacine or blocked by the NKCC1 inhibitor bumetanide. The developmental upregulation of the K-Cl cotransporter 2 (KCC2) was unperturbed, whereas the pharmacologically isolated glutamatergic network activity and the intrinsic excitability of CA3 pyramidal neurons were enhanced in the NKCC1(-/-) hippocampus. Hence, developmental expression of KCC2, unsilencing of AMPA-type synapses, and early network events can take place in the absence of excitatory GABAergic signaling in the neonatal hippocampus. Furthermore, we show that genetic as well as pharmacologically induced loss of NKCC1-dependent excitatory actions of GABA results in a dramatic compensatory increase in the intrinsic excitability of glutamatergic neurons, pointing to powerful homeostatic regulation of neuronal activity in the developing hippocampal circuitry. PMID- 19474326 TI - Role of neuroepithelial Sonic hedgehog in hypothalamic patterning. AB - The hypothalamus is a region of the diencephalon with particularly complex patterning. Sonic hedgehog (Shh), encoding a protein with key developmental roles, shows a peculiar and dynamic diencephalic expression pattern. Here, we use transgenic strategies and in vitro experiments to test the hypothesis that Shh expressed in the diencephalic neuroepithelium (neural Shh) coordinates tissue growth and patterning in the hypothalamus. Our results show that neural Shh coordinates anteroposterior and dorsoventral patterning in the hypothalamus and in the diencephalon-telencephalon junction. Neural Shh also coordinates mediolateral hypothalamic patterning, since it is necessary for the lateral hypothalamus to attain proper size and is required for the specification of hypocretin/orexin cells. Finally, neural Shh is necessary to maintain expression of differentiation markers including survival factor Foxb1. PMID- 19474327 TI - Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia. AB - Cerebral ischemia and reperfusion increase superoxide anions (O(2)(*-)) in brain mitochondria. Manganese superoxide dismutase (Mn-SOD; SOD2), a primary mitochondrial antioxidant enzyme, scavenges superoxide radicals and its overexpression provides neuroprotection. However, the regulatory mechanism of Mn SOD expression during cerebral ischemia and reperfusion is still unclear. In this study, we identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse Mn-SOD gene, and elucidated the mechanism of O(2)(*-) overproduction after transient focal cerebral ischemia (tFCI). We found that Mn-SOD expression is significantly reduced by reperfusion in the cerebral ischemic brain. We also found that activated STAT3 is usually recruited into the mouse Mn-SOD promoter and upregulates transcription of the mouse Mn-SOD gene in the normal brain. However, at early postreperfusion periods after tFCI, STAT3 was rapidly downregulated, and its recruitment into the Mn-SOD promoter was completely blocked. In addition, transcriptional activity of the mouse Mn-SOD gene was significantly reduced by STAT3 inhibition in primary cortical neurons. Moreover, we found that STAT3 deactivated by reperfusion induces accumulation of O(2)(*-) in mitochondria. The loss of STAT3 activity induced neuronal cell death by reducing Mn-SOD expression. Using SOD2-/+ heterozygous knock-out mice, we found that Mn-SOD is a direct target of STAT3 in reperfusion-induced neuronal cell death. Our study demonstrates that STAT3 is a novel transcription factor of the mouse Mn-SOD gene and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the mouse brain. PMID- 19474328 TI - Relationship among brain and blood glucose levels and spontaneous and glucoprivic feeding. AB - Although several studies implicate small declines in blood glucose levels as stimulus for spontaneous meal initiation, no mechanism is known for how these dips might initiate feeding. To assess the role of ventromedial hypothalamus (VMH) (arcuate plus ventromedial nucleus) glucosensing neurons as potential mediators of spontaneous and glucoprivic feeding, meal patterns were observed, and blood and VMH microdialysis fluid were sampled in 15 rats every 10 min for 3.5 h after dark onset and 2 h after insulin (5 U/kg, i.v.) infusion. Blood glucose levels declined by 11% beginning approximately 5 min before 65% of all spontaneous meals, with no fall in VMH levels. After insulin, blood and VMH glucose reached nadirs by 30-40 min, and the same rats ate 60% faster and spent 84% more time eating during the ensuing hypoglycemia. Although 83% of first hypoglycemic meals were preceded by 5 min dips in VMH (but not blood) glucose levels, neither blood nor VMH levels declined before second meals, suggesting that low glucose, rather than changing levels, was the stimulus for glucoprivic meals. Furthermore, altering VMH glucosensing by raising or lowering glucokinase (GK) activity failed to affect spontaneous feeding, body or adipose weights, or glucose tolerance. However, chronic depletion by 26-70% of VMH GK mRNA reduced glucoprivic feeding. Thus, although VMH glucosensing does not appear to be involved in either spontaneous feeding or long-term body-weight regulation, it does participate in glucoprivic feeding, similar to its role in the counter regulatory neurohumoral responses to glucoprivation. PMID- 19474329 TI - Subthreshold glutamate release from mitral cell dendrites. AB - The dendrites of a number of neuron types function as presynaptic structures, releasing transmitter after action potentials and dendritic spikes. In this regard, dendrites can function like axons, producing discrete outputs after suprathreshold electrical events. However, as the major site of synaptic inputs, dendrites experience ongoing subthreshold fluctuations in membrane potential, raising the question of whether these subthreshold changes can cause changes in transmitter release. Here, we show that mitral cells of the accessory olfactory bulb release glutamate from their dendrites in response to both subthreshold and suprathreshold stimuli. Whereas subthreshold output was typically low under control conditions, it could be enhanced several fold by pharmacological or endogenous activation of group I metabotropic glutamate receptors. These results indicate that presynaptic dendrites can support two distinct forms of output, and can dynamically regulate how electrical activity is coupled to transmitter release. PMID- 19474330 TI - Visual field map clusters in macaque extrastriate visual cortex. AB - The macaque visual cortex contains >30 different functional visual areas, yet surprisingly little is known about the underlying organizational principles that structure its components into a complete "visual" unit. A recent model of visual cortical organization in humans suggests that visual field maps are organized as clusters. Clusters minimize axonal connections between individual field maps that represent common visual percepts, with different clusters thought to carry out different functions. Experimental support for this hypothesis, however, is lacking in macaques, leaving open the question of whether it is unique to humans or a more general model for primate vision. Here we show, using high-resolution blood oxygen level-dependent functional magnetic resonance imaging data in the awake monkey at 7 T, that the middle temporal area (area MT/V5) and its neighbors are organized as a cluster with a common foveal representation and a circular eccentricity map. This novel view on the functional topography of area MT/V5 and satellites indicates that field map clusters are evolutionarily preserved and may be a fundamental organizational principle of the Old World primate visual cortex. PMID- 19474332 TI - Cerebral activity during the anesthesia-like state induced by mesopontine microinjection of pentobarbital. AB - Microinjection of pentobarbital into a restricted region of rat brainstem, the mesopontine tegmental anesthesia area (MPTA), induces a reversible anesthesia like state characterized by loss of the righting reflex, atonia, antinociception, and loss of consciousness as assessed by electroencephalogram synchronization. We examined cerebral activity during this state using FOS expression as a marker. Animals were anesthetized for 50 min with a series of intracerebral microinjections of pentobarbital or with systemic pentobarbital and intracerebral microinjections of vehicle. FOS expression was compared with that in awake animals microinjected with vehicle. Neural activity was suppressed throughout the cortex whether anesthesia was induced by systemic or MPTA routes. Changes were less consistent subcortically. In the zona incerta and the nucleus raphe pallidus, expression was strongly suppressed during systemic anesthesia, but only mildly during MPTA-induced anesthesia. Dissociation was seen in the tuberomammillary nucleus where suppression occurred during systemic-induced anesthesia only, and in the lateral habenular nucleus where activity was markedly increased during systemic-induced anesthesia but not following intracerebral microinjection. Several subcortical nuclei previously associated with cerebral arousal were not affected. In the MPTA itself FOS expression was suppressed during systemic anesthesia. Differences in the pattern of brain activity in the two modes of anesthesia are consistent with the possibility that anesthetic endpoints might be achieved by alternative mechanisms: direct drug action for systemic anesthesia or via ascending pathways for MPTA-induced anesthesia. However, it is also possible that systemically administered agents induce anesthesia, at least in part, by a primary action in the MPTA with cortical inhibition occurring secondarily. PMID- 19474331 TI - Transcriptional and electrophysiological maturation of neocortical fast-spiking GABAergic interneurons. AB - Fast-spiking (FS) interneurons are important elements of neocortical circuitry that constitute the primary source of synaptic inhibition in adult cortex and impart temporal organization on ongoing cortical activity. The highly specialized intrinsic membrane and firing properties that allow cortical FS interneurons to perform these functions are attributable to equally specialized gene expression, which is ultimately coordinated by cell-type-specific transcriptional regulation. Although embryonic transcriptional events govern the initial steps of cell-type specification in most cortical interneurons, including FS cells, the electrophysiological properties that distinguish adult cortical cell types emerge relatively late in postnatal development, and the transcriptional events that drive this maturational process are not known. To address this, we used mouse whole-genome microarrays and whole-cell patch clamp to characterize the transcriptional and electrophysiological maturation of cortical FS interneurons between postnatal day 7 (P7) and P40. We found that the intrinsic and synaptic physiology of FS cells undergoes profound regulation over the first 4 postnatal weeks and that these changes are correlated with primarily monotonic but bidirectional transcriptional regulation of thousands of genes belonging to multiple functional classes. Using our microarray screen as a guide, we discovered that upregulation of two-pore K(+) leak channels between P10 and P25 contributes to one of the major differences between the intrinsic membrane properties of immature and adult FS cells and found a number of other candidate genes that likely confer cell-type specificity on mature FS cells. PMID- 19474333 TI - Realignment of interaural cortical maps in asymmetric hearing loss. AB - Misalignment of interaural cortical response maps in asymmetric hearing loss evolves from initial gross divergence to near convergence over a 6 month recovery period. The evolution of left primary auditory cortex (AI) interaural frequency map changes is chronicled in squirrel monkeys with asymmetric hearing loss induced by overstimulating the right ear with a 1 kHz tone at 136 dB for 3 h. AI frequency response areas (FRAs), derived from tone bursts presented to the poorer or better hearing ears, are compared at 6, 12, and 24 weeks after acoustic overstimulation. Characteristic frequency (CF) and minimum threshold parameters are extracted from FRAs, and they are used to quantify interaural response map differences. A large interaural CF map misalignment of DeltaCF approximately 1.27 octaves at 6 weeks after overstimulation decreases substantially to DeltaCF approximately 0.62 octave at 24 weeks. Interaural cortical threshold map misalignment faithfully reflects peripheral asymmetric hearing loss at 6 and 12 weeks. However, AI threshold map misalignment essentially disappears at 24 weeks, primarily because ipsilateral cortical thresholds have become unexpectedly elevated relative to peripheral thresholds. The findings document that plastic change in central processing of sound stimuli arriving from the nominally better hearing ear may account for progressive realignment of both interaural frequency and threshold maps. PMID- 19474334 TI - Laminar fate and phenotype specification of cerebellar GABAergic interneurons. AB - In most CNS regions, the variety of inhibitory interneurons originates from separate pools of progenitors residing in discrete germinal domains, where they become committed to specific phenotypes and positions during their last mitosis. We show here that GABAergic interneurons of the rodent cerebellum are generated through a different mechanism. Progenitors for these interneurons delaminate from the ventricular neuroepithelium of the embryonic cerebellar primordium and continue to proliferate in the prospective white matter during late embryonic and postnatal development. Young postmitotic interneurons do not migrate immediately to their final destination, but remain in the prospective white matter for several days. The different interneuron categories are produced according to a continuous inside-out positional sequence, and cell identity and laminar placement in the cerebellar cortex are temporally related to birth date. However, terminal commitment does not occur while precursors are still proliferating, and postmitotic cells heterochronically transplanted to developing cerebella consistently adopt host-specific phenotypes and positions. However, solid grafts of prospective white matter implanted into the adult cerebellum, when interneuron genesis has ceased, produce interneuron types characteristic of the donor age. Therefore, specification of cerebellar GABAergic interneurons occurs through a hitherto unknown process, in which postmitotic neurons maintain broad developmental potentialities and their phenotypic choices are dictated by instructive cues provided by the microenvironment of the prospective white matter. Whereas in most CNS regions the repertoire of inhibitory interneurons is produced by recruiting precursors from different origins, in the cerebellum it is achieved by creating phenotypic diversity from a single source. PMID- 19474335 TI - Pannexin 1: the molecular substrate of astrocyte "hemichannels". AB - Purinergic signaling plays distinct and important roles in the CNS, including the transmission of calcium signals between astrocytes. Gap junction hemichannels are among the mechanisms proposed by which astrocytes might release ATP; however, whether the gap junction protein connexin43 (Cx43) forms these "hemichannels" remains controversial. Recently, a new group of proteins, the pannexins, have been shown to form nonselective, high-conductance plasmalemmal channels permeable to ATP, thereby offering an alternative for the hemichannel protein. Here, we provide strong evidence that, in cultured astrocytes, pannexin1 (Panx1) but not Cx43 forms hemichannels. Electrophysiological and fluorescence microscope recordings performed in wild-type and Cx43-null astrocytes did not reveal any differences in hemichannel activity, which was mostly eliminated by treating Cx43 null astrocytes with Panx1-short interfering RNA [Panx1-knockdown (Panx1-KD)]. Moreover, quantification of the amount of ATP released from wild-type, Cx43-null, and Panx1-KD astrocytes indicates that downregulation of Panx1, but not of Cx43, prevented ATP release from these cells. PMID- 19474336 TI - In mice lacking V2a interneurons, gait depends on speed of locomotion. AB - Many animals are capable of changing gait with speed of locomotion. The neural basis of gait control and its dependence on speed are not fully understood. Mice normally use a single "trotting" gait while running at all speeds, either over ground or on a treadmill. Transgenic mouse mutants in which the trotting is replaced by hopping also lack a speed-dependent change in gait. Here we describe a transgenic mouse model in which the V2a interneurons have been ablated by targeted expression of diphtheria toxin A chain (DTA) under the control of the Chx10 gene promoter (Chx10::DTA mice). Chx10::DTA mice show normal trotting gait at slow speeds but transition to a galloping gait as speed increases. Although left-right limb coordination is altered in Chx10::DTA mice at fast speed, alternation of forelegs and hindlegs and the relative duration of swing and stance phases for individual limbs is unchanged compared with wild-type mice. The speed-dependent loss of left-right alternation is recapitulated during drug induced fictive locomotion in spinal cords isolated from neonatal Chx10::DTA mice, and high-speed fictive locomotion evoked by caudal spinal cord stimulation also shows synchronous left-right bursting. These results show that spinal V2a interneurons are required for maintaining left-right alternation at high speeds. Whether animals that generate galloping or hopping gaits, characterized by synchronous movement of left and right forelegs and hindlegs, have lost or modified the function of V2a interneurons is an intriguing question. PMID- 19474337 TI - PathExpress update: the enzyme neighbourhood method of associating gene expression data with metabolic pathways. AB - The post-genomic era presents us with the challenge of linking the vast amount of raw data obtained with transcriptomic and proteomic techniques to relevant biological pathways. We present an update of PathExpress, a web-based tool to interpret gene-expression data and explore the metabolic network without being restricted to predefined pathways. We define the Enzyme Neighbourhood (EN) as a sub-network of linked enzymes with a limited path length to identify the most relevant sub-networks affected in gene-expression experiments. PathExpress is freely available at: http://bioinfoserver.rsbs.anu.edu.au/utils/PathExpress/. PMID- 19474338 TI - PLecDom: a program for identification and analysis of plant lectin domains. AB - PLecDom is a program for detection of Plant Lectin Domains in a polypeptide or EST sequence, followed by a classification of the identified domains into known families. The web server is a collection of plant lectin domain families represented by alignments and profile Hidden Markov Models. PLecDom was developed after a rigorous analysis of evolutionary relationships between available sequences of lectin domains with known specificities. Users can test their sequences for potential lectin domains, catalog the identified domains into broad substrate classes, estimate the extent of divergence of new domains with existing homologs, extract domain boundaries and examine flanking sequences for further analysis. The high prediction accuracy of PLecDom combined with the ease with which it handles large scale input, enabled us to apply the program to protein and EST data from 48 plant genome-sequencing projects in various stages of completion. Our results represent a significant enrichment of the currently annotated plant lectins, and highlight potential targets for biochemical characterization. The search algorithm requires input in fasta format and is designed to process simultaneous connection requests from multiple users, such that huge sets of input sequences can be scanned in a matter of seconds. PLecDom is available at http://www.nipgr.res.in/plecdom.html. PMID- 19474339 TI - Web 3DNA--a web server for the analysis, reconstruction, and visualization of three-dimensional nucleic-acid structures. AB - The w3DNA (web 3DNA) server is a user-friendly web-based interface to the 3DNA suite of programs for the analysis, reconstruction, and visualization of three dimensional (3D) nucleic-acid-containing structures, including their complexes with proteins and other ligands. The server allows the user to determine a wide variety of conformational parameters in a given structure--such as the identities and rigid-body parameters of interacting nucleic-acid bases and base-pair steps, the nucleotides comprising helical fragments, etc. It is also possible to build 3D models of arbitrary nucleotide sequences and helical types, customized single stranded and double-helical structures with user-defined base-pair parameters and sequences, and models of DNA 'decorated' at user-defined sites with proteins and other molecules. The visualization component offers unique, publication-quality representations of nucleic-acid structures, such as 'block' images of bases and base pairs and stacking diagrams of interacting nucleotides. The w3DNA web server, located at http://w3dna.rutgers.edu, is free and open to all users with no login requirement. PMID- 19474340 TI - Efficient silencing of gene expression with modular trimeric Pol II expression cassettes comprising microRNA shuttles. AB - Expressed polycistronic microRNA (miR) cassettes have useful properties that can be utilized for RNA interference (RNAi)-based gene silencing. To advance their application we generated modular trimeric anti-hepatitis B virus (HBV) Pol II cassettes encoding primary (pri)-miR-31-derived shuttles that target three different viral genome sites. A panel of six expression cassettes, comprising each of the possible ordering combinations of the pri-miR-31 shuttles, was initially tested. Effective silencing of individual target sequences was achieved in transfected cells and transcribed pri-miR trimers generated intended guide strands. There was, however, variation in processing and silencing by each of the shuttles. In some cases the monomers' position within the trimers influenced processing and this correlated with target silencing. Compromised efficacy could be compensated by substituting the pri-miR-31 backbone with a pri-miR-30a scaffold. Inhibition of HBV replication was achieved in vivo, and in cell culture without disruption of endogenous miR function or induction of the interferon response. A mutant HBV target sequence, with changes in one of the guide cognates, was also silenced by the trimeric cassettes. The modular nature of the cassettes together with compatibility with expression from Pol II promoters should be advantageous for gene silencing applications requiring simultaneous targeting of different sites. PMID- 19474341 TI - A conformational change in the helicase core is necessary but not sufficient for RNA unwinding by the DEAD box helicase YxiN. AB - Cooperative binding of ATP and RNA to DEAD-box helicases induces the closed conformation of their helicase core, with extensive interactions across the domain interface. The bound RNA is bent, and its distortion may constitute the first step towards RNA unwinding. To dissect the role of the conformational change in the helicase core for RNA unwinding, we characterized the RNA stimulated ATPase activity, RNA unwinding and the propensity to form the closed conformer for mutants of the DEAD box helicase YxiN. The ATPase-deficient K52Q mutant forms a closed conformer upon binding of ATP and RNA, but is deficient in RNA unwinding. A mutation in motif III slows down the catalytic cycle, but neither affects the propensity for the closed conformer nor its global conformation. Hence, the closure of the cleft in the helicase core is necessary but not sufficient for RNA unwinding. In contrast, the G303A mutation in motif V prevents a complete closure of the inter-domain cleft, affecting ATP binding and hydrolysis and is detrimental to unwinding. Possibly, the K52Q and motif III mutants still introduce a kink into the backbone of bound RNA, whereas G303A fails to kink the RNA substrate. PMID- 19474342 TI - Using high-density exon arrays to profile gene expression in closely related species. AB - Global comparisons of gene expression profiles between species provide significant insight into gene regulation, evolutionary processes and disease mechanisms. In this work, we describe a flexible and intuitive approach for global expression profiling of closely related species, using high-density exon arrays designed for a single reference genome. The high-density probe coverage of exon arrays allows us to select identical sets of perfect-match probes to measure expression levels of orthologous genes. This eliminates a serious confounding factor in probe affinity effects of species-specific microarray probes, and enables direct comparisons of estimated expression indexes across species. Using a newly designed Affymetrix exon array, with eight probes per exon for approximately 315,000 exons in the human genome, we conducted expression profiling in corresponding tissues from humans, chimpanzees and rhesus macaques. Quantitative real-time PCR analysis of differentially expressed candidate genes is highly concordant with microarray data, yielding a validation rate of 21/22 for human versus chimpanzee differences, and 11/11 for human versus rhesus differences. This method has the potential to greatly facilitate biomedical and evolutionary studies of gene expression in nonhuman primates and can be easily extended to expression array design and comparative analysis of other animals and plants. PMID- 19474343 TI - The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators. AB - LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upregulated during bacterial-host cell contact. Here, we report the crystal structures of both regulatory domain and full-length CrgA, the first of a novel subclass of LTTRs that form octameric rings. Non-denaturing mass spectrometry analysis and analytical ultracentrifugation established that the octameric form of CrgA is the predominant species in solution in both the presence and absence of an oligonucleotide encompassing the CrgA-binding sequence. Furthermore, analysis of the isolated CrgA-DNA complex by mass spectrometry showed stabilization of a double octamer species upon DNA binding. Based on the observed structure and the mass spectrometry findings, a model is proposed in which a hexadecameric array of two CrgA oligomers binds to its DNA target site. PMID- 19474345 TI - This paper has been retracted.Retraction notice is found at http://nar.oxfordjournals.org/cgi/content/full/37/15/5234. PMID- 19474344 TI - Methylation detection oligonucleotide microarray analysis: a high-resolution method for detection of CpG island methylation. AB - Methylation of CpG islands associated with genes can affect the expression of the proximal gene, and methylation of non-associated CpG islands correlates to genomic instability. This epigenetic modification has been shown to be important in many pathologies, from development and disease to cancer. We report the development of a novel high-resolution microarray that detects the methylation status of over 25,000 CpG islands in the human genome. Experiments were performed to demonstrate low system noise in the methodology and that the array probes have a high signal to noise ratio. Methylation measurements between different cell lines were validated demonstrating the accuracy of measurement. We then identified alterations in CpG islands, both those associated with gene promoters, as well as non-promoter-associated islands in a set of breast and ovarian tumors. We demonstrate that this methodology accurately identifies methylation profiles in cancer and in principle it can differentiate any CpG methylation alterations and can be adapted to analyze other species. PMID- 19474346 TI - AutoClass@IJM: a powerful tool for Bayesian classification of heterogeneous data in biology. AB - Recently, several theoretical and applied studies have shown that unsupervised Bayesian classification systems are of particular relevance for biological studies. However, these systems have not yet fully reached the biological community mainly because there are few freely available dedicated computer programs, and Bayesian clustering algorithms are known to be time consuming, which limits their usefulness when using personal computers. To overcome these limitations, we developed AutoClass@IJM, a computational resource with a web interface to AutoClass, a powerful unsupervised Bayesian classification system developed by the Ames Research Center at N.A.S.A. AutoClass has many powerful features with broad applications in biological sciences: (i) it determines the number of classes automatically, (ii) it allows the user to mix discrete and real valued data, (iii) it handles missing values. End users upload their data sets through our web interface; computations are then queued in our cluster server. When the clustering is completed, an URL to the results is sent back to the user by e-mail. AutoClass@IJM is freely available at: http://ytat2.ijm.univ-paris diderot.fr/AutoclassAtIJM.html. PMID- 19474347 TI - Physical and functional interactions between Escherichia coli MutL and the Vsr repair endonuclease. AB - DNA mismatch repair (MMR) and very-short patch (VSP) repair are two pathways involved in the repair of T:G mismatches. To learn about competition and cooperation between these two repair pathways, we analyzed the physical and functional interaction between MutL and Vsr using biophysical and biochemical methods. Analytical ultracentrifugation reveals a nucleotide-dependent interaction between Vsr and the N-terminal domain of MutL. Using chemical crosslinking, we mapped the interaction site of MutL for Vsr to a region between the N-terminal domains similar to that described before for the interaction between MutL and the strand discrimination endonuclease MutH of the MMR system. Competition between MutH and Vsr for binding to MutL resulted in inhibition of the mismatch-provoked MutS- and MutL-dependent activation of MutH, which explains the mutagenic effect of Vsr overexpression. Cooperation between MMR and VSP repair was demonstrated by the stimulation of the Vsr endonuclease in a MutS-, MutL- and ATP-hydrolysis-dependent manner, in agreement with the enhancement of VSP repair by MutS and MutL in vivo. These data suggest a mobile MutS-MutL complex in MMR signalling, that leaves the DNA mismatch prior to, or at the time of, activation of downstream effector molecules such as Vsr or MutH. PMID- 19474348 TI - Directed evolution of an orthogonal nucleoside analog kinase via fluorescence activated cell sorting. AB - Nucleoside analogs (NAs) represent an important category of prodrugs for the treatment of viral infections and cancer, yet the biological potency of many analogs is compromised by their inefficient activation through cellular 2' deoxyribonucleoside kinases (dNKs). We herein report the directed evolution and characterization of an orthogonal NA kinase for 3'-deoxythymidine (ddT), using a new FACS-based screening protocol in combination with a fluorescent analog of ddT. Four rounds of random mutagenesis and DNA shuffling of Drosophila melanogaster 2'-deoxynucleoside kinase, followed by FACS analysis, yielded an orthogonal ddT kinase with a 6-fold higher activity for the NA and a 20-fold k(cat)/K(M) preference for ddT over thymidine, an overall 10,000-fold change in substrate specificity. The contributions of individual amino acid substitutions in the ddT kinase were evaluated by reverse engineering, enabling a detailed structure-function analysis to rationalize the observed changes in performance. Based on our results, kinase engineering with fluorescent NAs and FACS should prove a highly versatile method for evolving selective kinase:NA pairs and for studying fundamental aspects of the structure-function relationship in dNKs. PMID- 19474349 TI - High-affinity triplex targeting of double stranded DNA using chemically modified peptide nucleic acid oligomers. AB - While sequence-selective dsDNA targeting by triplex forming oligonucleotides has been studied extensively, only very little is known about the properties of PNA dsDNA triplexes--mainly due to the competing invasion process. Here we show that when appropriately modified using pseudoisocytosine substitution, in combination with (oligo)lysine or 9-aminoacridine conjugation, homopyrimidine PNA oligomers bind complementary dsDNA targets via triplex formation with (sub)nanomolar affinities (at pH 7.2, 150 mM Na(+)). Binding affinity can be modulated more than 1000-fold by changes in pH, PNA oligomer length, PNA net charge and/or by substitution of pseudoisocytosine for cytosine, and conjugation of the DNA intercalator 9-aminoacridine. Furthermore, 9-aminoacridine conjugation also strongly enhanced triplex invasion. Specificity for the fully matched target versus one containing single centrally located mismatches was more than 150-fold. Together the data support the use of homopyrimidine PNAs as efficient and sequence selective tools in triplex targeting strategies under physiological relevant conditions. PMID- 19474350 TI - Construction and functional analyses of a comprehensive sigma54 site-directed mutant library using alanine-cysteine mutagenesis. AB - The sigma(54) factor associates with core RNA polymerase (RNAP) to form a holoenzyme that is unable to initiate transcription unless acted on by an activator protein. sigma(54) is closely involved in many steps of activator dependent transcription, such as core RNAP binding, promoter recognition, activator interaction and open complex formation. To systematically define sigma(54) residues that contribute to each of these functions and to generate a resource for site specific protein labeling, a complete mutant library of sigma(54) was constructed by alanine-cysteine scanning mutagenesis. Amino acid residues from 3 to 476 of Cys(-)sigma(54) were systematically mutated to alanine and cysteine in groups of two adjacent residues at a time. The influences of each substitution pair upon the functions of sigma(54) were analyzed in vivo and in vitro and the functions of many residues were revealed for the first time. Increased sigma(54) isomerization activity seldom corresponded with an increased transcription activity of the holoenzyme, suggesting the steps after sigma(54) isomerization, likely to be changes in core RNAP structure, are also strictly regulated or rate limiting to open complex formation. A linkage between core RNAP binding activity and activator responsiveness indicates that the sigma(54)-core RNAP interface changes upon activation. PMID- 19474352 TI - Histological patterns in drug-induced liver disease. AB - The diagnosis of drug-induced liver injury (DILI) is a challenging problem, often confounded by incomplete clinical information and the difficulty of eliciting exposure to herbal products, over-the-counter agents and toxins. The task is further rendered difficult on biopsy, as drugs can mimic all the patterns found in primary liver disease. Acute hepatitis, with or without cholestasis, is the most common histological pattern of DILI, and drugs such as acetaminophen are the leading causes of acute liver failure. Most cases of DILI resolve on discontinuation of the drug, but recovery can take months or rarely the disease can progress despite drug withdrawal. Drugs such as methotrexate can lead to chronic hepatitis and cirrhosis, while others such as minocycline, nitrofurantoin and methyldopa are implicated in autoimmune hepatitis. Prolonged cholestasis and ductopenia resembling primary chronic biliary disease can occur. Drug-induced steatohepatitis is also an uncommon pattern, but is well described with drugs such as amiodarone and irinotecan. In the presence of risk factors such as obesity and diabetes, some drugs such as tamoxifen, oestrogens and nifedipine can precipitate or exacerbate steatohepatitis. Other observed patterns include granulomatous hepatitis, vascular injury (eg, sinusoidal obstruction syndrome), Ito cell lipidosis and neoplasms (eg, adenomas). PMID- 19474351 TI - A biochemically active MCM-like helicase in Bacillus cereus. AB - The mini-chromosome maintenance (MCM) proteins serve as the replicative helicases in archaea and eukaryotes. Interestingly, an MCM homolog was identified, by BLAST analysis, within a phage integrated in the bacterium Bacillus cereus (Bc). BcMCM is only related to the AAA region of MCM-helicases; the typical amino-terminus is missing and is replaced by a segment with weak homology to primases. We show that BcMCM displays 3'-->5' helicase and ssDNA-stimulated ATPase activity, properties that arise from its conserved AAA domain. Isolated BcMCM is a monomer in solution but likely forms the functional oligomer in vivo. We found that the BcMCM amino terminus can bind ssDNA and harbors a zinc atom, both hallmarks of the typical MCM amino-terminus. No BcMCM-catalyzed primase activity could be detected. We propose that the divergent amino-terminus of BcMCM is a paralog of the corresponding region of MCM-helicases. A divergent amino terminus makes BcMCM a useful model for typical MCM-helicases since it accomplishes the same function using an apparently unrelated structure. PMID- 19474353 TI - Renal toxicity of therapeutic drugs. AB - A number of therapeutic agents can adversely affect the kidney, resulting in tubulointerstitial, glomerular or vascular disease. Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often cause by antibiotics or non-steroidal anti-inflammatory drugs. Drug-induced glomerular and vascular disease is relatively rare. This review describes the morphological patterns of drug-induced disease in the kidney. The histopathological changes are often similar to disease that is idiopathic or due to other causes, so that awareness and clinical correlation are most helpful to arrive at the aetiology. PMID- 19474354 TI - HER-2/neu analysis in breast cancer bone metastases. AB - BACKGROUND: HER-2 is the target for antibody-based treatment of breast cancer (trastuzumab), which is highly successful in both advanced disease and the adjuvant setting. HER-2 can be analysed by fluorescence in situ hybridisation (FISH) for gene amplification or immunohistochemistry (IHC) for protein overexpression. AIM: As both methods are known to be influenced by previous tissue processing, to analyse the applicability of both FISH and IHC to decalcified bone metastases of breast cancer. METHODS: A tissue microarray (TMA) was constructed from 149 breast cancer bone metastases. Consecutive TMA sections were analysed by FISH (PathVysion) and IHC (HercepTest). RESULTS: FISH analysis was interpretable in 113 (85.0%) cases. Amplification was seen in 14 (12.4%) interpretable metastases. HER-2 positivity on IHC analysis was 3+ in 9.8% of cases and 2+ in 11.3%. A comparison of the two techniques revealed high concordance. Of the 14 cases of amplification, 10 (71%) showed 3+ IHC staining, two (14%) showed 2+, one (7%) showed 1+, and one (7%) showed 0+. Three of the four amplified cases that did not show 3+ IHC staining had an equivocal FISH result, with a HER-2/centromere 17 ratio of 1.8-2.2. Of the 13 cases that showed IHC 3+ staining, amplification was present in 10 (77%). CONCLUSIONS: HER-2 FISH analysis has an excellent success rate in highly standardised EDTA-decalcified bone metastases, suggesting that this method is easily applicable to decalcified tissues. The high concordance between IHC and FISH suggests that HER-2 IHC may be equally applicable to EDTA-treated tissues as to the usual formalin-fixed tissues. PMID- 19474355 TI - Call for a European programme in external quality assurance for bone marrow immunohistochemistry; report of a European Bone Marrow Working Group pilot study. AB - BACKGROUND AND AIMS: In diagnostic immunohistochemistry (IHC), daily quality control/quality assurance measures (QC/QA) and participation in external quality assurance programmes (EQA) are important in ensuring good laboratory practice and patient care. Bone marrow trephine biopsies (BMTB) have been generally excluded from EQA programmes for diagnostic IHC due to a lack of standards for tissue processing. The European Bone Marrow Working Group (EBMWG) has set up an EBMWG IHC Committee with the task of exploring the plausibility of an EQA programme for BMTB IHC in Europe. METHODS: 28 laboratories participated in a web-based anonymous survey; 19 laboratories submitted a total of 109 slides stained for CD34, CD117, CD20, CD3, Ki-67 and a megakaryocyte marker of choice. RESULTS: Eight different fixatives and nine different decalcification methods were used. While 93% of participants believed that they produced excellent results in BMTB IHC, only 4/19 (21%) laboratories did not have any poor results. CD117 and Ki-67, with 53% and 50% poor results, respectively, were the most problematic immunostains, while CD20 was the least problematic, with only 11% poor results. CONCLUSIONS: The EBMWG IHC Committee calls for a reduction in the tissue processing methods for BMTB and establishment of an EQA programme for BMTB IHC to help diagnostic IHC laboratories calibrate their tests according to expert recommendations. This is especially necessary in the light of recent introduction of predictive IHC tests in BMTB. PMID- 19474356 TI - Spindle cell tumour with glandular elements: an unusual ileal neoplasm. AB - This report describes a tumour in the ileum with clinical features initially suggestive of a gastrointestinal stromal tumour (GIST). Histopathological examination revealed a biphasic tumour in which the spindle cell component showed immunohistochemical evidence of smooth muscle differentiation but without the characteristic profile of a GIST. A well-differentiated epithelial component was also present, comprising glandular structures with immunohistochemical features suggestive of Mullerian differentiation. Similar glandular differentiation has been described in uterine leiomyomas but not, to our knowledge, in tumours associated with the small bowel. None of the characteristic mutations of GISTs were identified in this case. There were no overt features of malignancy but, because of the unusual nature of the case, we assessed the biological behaviour as uncertain. PMID- 19474357 TI - Adenofibroma of the testis. AB - Adenofibromas of the testicular parenchyma are exceptional with only one case published in the literature. Whereas adenofibromas of mullerian derivatives are well described, testicular tumours resembling surface ovarian epithelium are rare. We describe a case of adenofibroma discovered incidentally while investigating for a hydrocoele in a 57-year-old patient. Histological and immunohistochemical evaluation confirmed the lesion as being a serous adenofibroma with immunohistochemical properties analogous to its ovarian counterpart. These lesions are to be considered in the differential diagnosis of unusual cystic lesions of the testis, in order not to confuse it with more sinister pathology. PMID- 19474358 TI - Road traffic accident fatalities: 1961 to 1986. AB - The various trauma-induced pathologies found at necropsy following road traffic accidents in the Bassetlaw area of Nottinghamshire from 1961 to 1986 were recorded and related to the time of death. The catchment area was mainly rural, including stretches of the A1 and A57, but included two small towns (Worksop and Retford). Pick up times varied considerably depending on the site of the accident, extraction procedures and ambulance journey distance. PMID- 19474359 TI - CD4 expression by mast cells in mastocytosis: a case report. AB - A 59-year-old man presented with a five-year history of an asymptomatic widespread truncal rash. Cutaneous biopsies showed mastocytosis, which was shown to be CD4-positive immunohistochemically. This potential diagnostic pitfall in the discrimination of mastocytosis from a variety of other haematopoietic neoplasms, particularly mycosis fungoides, is discussed. PMID- 19474361 TI - Fatal Addison's disease in a teenager. PMID- 19474362 TI - Pitfall in frozen section diagnosis of unusually located gelatinous cardiac tumour. PMID- 19474363 TI - Greater abundance of extracellular Leishmania donovani bodies: possible clue from comparison of bone marrow aspirate and imprint findings. PMID- 19474364 TI - Benford's law in relation to terminal digit preference. PMID- 19474365 TI - Will histopathology survive in Pakistan? PMID- 19474368 TI - Microwave ablation compared with radiofrequency ablation in lung tissue-is microwave not just for popcorn anymore? AB - In this issue of Radiology, Brace et al (1) showed that, compared with radiofrequency (RF) ablation, larger and more circular zones of thermal necrosis with faster growth of the ablation zone can be achieved with microwave ablation in a swine lung model. To my knowledge, this study is the first comparison of these ablation modalities in the lung and, given the observed differences, future clinical trials for evaluation of available technologies for the treatment of patients with pulmonary neoplasms are warranted. PMID- 19474369 TI - Acute stroke triage to intravenous thrombolysis and other therapies with advanced CT or MR imaging: pro CT. PMID- 19474370 TI - Acute stroke triage to intravenous thrombolysis and other therapies with advanced CT or MR imaging: pro MR imaging. PMID- 19474371 TI - Computer-aided detection evaluation methods are not created equal. PMID- 19474372 TI - The appropriateness of imaging: a comprehensive conceptual framework. AB - This review seeks to clarify and explicate an elusive concept: the appropriateness of diagnostic imaging. To ensure a common basis for discussion, several key components are articulated and defined. These include the diagnostic imaging procedure (DIP) itself, the subject (a patient), and the setting (a clinical scenario) in which the DIP is being considered. A review of the literature shows that appropriateness is a logical extension of empiric research, which has revealed substantial variation in the type and intensity of health services delivered to otherwise similar populations and communities in the United States. Against this background, the appropriate rate of a service in a population is transformed into appropriateness for an individual patient, which, when defined in terms of expected net health outcome, provides a conceptual link with the denominator of cost-effectiveness analysis. The complementary roles of clinical trials, technology assessment, decision-analytic modeling, and consensus methods in estimating appropriateness are compared and contrasted. PMID- 19474373 TI - Can compression be reduced for breast tomosynthesis? Monte carlo study on mass and microcalcification conspicuity in tomosynthesis. AB - PURPOSE: To assess, in a voxelized anthropomorphic breast phantom, how the conspicuity of breast masses and microcalcifications may be affected by applying reduced breast compression in tomosynthesis. MATERIALS AND METHODS: A breast tomosynthesis system was modeled by using a Monte Carlo program and a voxelized anthropomorphic breast phantom. The Monte Carlo program created simulated tomosynthesis projection images, which were reconstructed by using filtered back projection software. Reconstructed images were analyzed for mass and microcalcification conspicuity, or the ratio of the lesion contrast to the anatomic and quantum noise surrounding the lesion. This analysis was performed at two compression levels (standard and 12.5% reduction) and for two breast compression thicknesses (4 and 6 cm). The change in conspicuity was analyzed for significance by using a bootstrap method and a paired Student t test. RESULTS: While keeping the glandular radiation dose constant with respective standard and reduced compression levels, the mean mass conspicuities were 1.39 +/- 0.15 (standard error of the mean) and 1.46 +/- 0.22 for a 4-cm breast compression phantom and 1.26 +/- 0.15 and 1.22 +/- 0.20 for a 6-cm breast phantom, and the mean microcalcification conspicuities were 16.2 +/- 2.87 and 18.6 +/- 2.63 for a 4-cm breast phantom and 11.4 +/- 1.11 and 10.6 +/- 1.18 for a 6-cm breast compression phantom. CONCLUSION: For constant glandular dose, mass and microcalcification conspicuity remained approximately constant with decreased compression. Constant conspicuity implies that reduced compression would have a minimal effect on radiologists' performance, which suggests that there is justification for a measured reduction of breast compression for breast tomosynthesis, increasing the comfort of women undergoing the examination. PMID- 19474374 TI - Survey of radiologists' knowledge regarding the management of severe contrast material-induced allergic reactions. AB - PURPOSE: To evaluate radiologists' knowledge of the appropriate management of severe contrast material-induced allergic reactions by means of a telephone survey. MATERIALS AND METHODS: Institutional research ethics board approval was obtained. Following verbal consent, a telephone survey of radiologists working in Canada's 13 English-speaking and 13 U.S. university-affiliated radiology departments was performed. Participants were selected by using a multistage sampling scheme and simple random sampling within departments. Given a severe contrast material-induced allergic reaction case scenario, radiologists were first asked their initial medication of choice, then questioned specifically on the use of epinephrine. The Canadian and U.S. cohorts were compared by using the chi(2) and Fisher exact tests, as appropriate, and proportions and 95% confidence intervals (CIs) were computed. RESULTS: A total of 253 (81%) of 311 radiologists from a 30% target population were surveyed. Ninety-one percent (231 of 253; 95% CI: 88%, 94%) of radiologists chose epinephrine as the most important initial medication. No radiologist gave the ideal response, but 41% (94 of 231; 95% CI: 35%, 47%) provided an acceptable administration route, concentration, and dose; 17% (n = 39; 95% CI: 12%, 22%) of radiologists provided an overdose. Only 11% (27 of 253; 95% CI: 7%, 15%) of radiologists knew what concentration of epinephrine was available in their drug kit and/or crash cart and what equipment would be required to administer it to a patient. CONCLUSION: Radiologists' knowledge of epinephrine for the management of severe contrast material-induced allergic reactions is deficient. PMID- 19474375 TI - FN13762 murine breast cancer: region-by-region correlation of first-pass perfusion CT indexes with histologic vascular parameters. AB - PURPOSE: To investigate the correlation between first-pass perfusion computed tomographic (CT) indexes and histologic vascular parameters in FN13762 breast cancer in rats by using region-by-region correlation methods. MATERIALS AND METHODS: The Animal Care and Use Committee approved this study. FN13762 murine breast cancer cells were implanted in 14 female Fischer 344 rats, and first-pass perfusion CT was performed. CT perfusion maps depicting blood flow, blood volume, mean transit time (MTT), and permeability-surface area (PSA) product were generated by using commercial perfusion software. The entire tumor area was divided into six separate regions on perfusion maps, and the regional perfusion indexes were quantified. Histologic vascular parameters, including microvessel density (MVD), luminal vessel number, luminal vessel area, and luminal vessel perimeter, were measured in the histologic region corresponding to the perfusion maps. Correlation analysis was performed between regional tumor perfusion indexes and histologic vascular parameters of the corresponding tumor region. Additionally, mean perfusion values of the entire tumor were correlated with histologic vascular parameters of the hot spot within the tumor. Among 14 rats, four were excluded from the analysis, and results were based on a final total of 10 rats. RESULTS: In tumors, blood flow, blood volume, and PSA product were significantly higher and MTT was significantly shorter (P < .05 for all) than these values in normal neck muscles. At region-by-region correlation, regional blood flow (r = 0.476), blood volume (r = 0.348), and MTT (r = -0.506) were significantly correlated with MVD in the corresponding tumor region (P < .01 for all). After adjustment for biologic variability between rats, regional blood flow (r = 0.614), blood volume (r = 0.515), MTT (r = -0.524), and PSA product (r = 0.228) remained significantly correlated with MVD in the corresponding tumor region. Correlation analysis between CT perfusion indexes of the entire tumor and histologic vascular parameters of the hot spot did not show significant correlations (P > .05). CONCLUSION: Regional blood flow, blood volume, and MTT are significantly correlated with MVD in the corresponding tumor region. PMID- 19474376 TI - Does arterial spin-labeling MR imaging-measured tumor perfusion correlate with renal cell cancer response to antiangiogenic therapy in a mouse model? AB - PURPOSE: To determine whether arterial spin-labeling (ASL) magnetic resonance (MR) imaging findings at baseline and early during antiangiogenic therapy can predict later resistance to therapy. MATERIALS AND METHODS: Protocol was approved by an institutional animal care and use committee. Caki-1, A498, and 786-0 human renal cell carcinoma (RCC) xenografts were implanted in 39 nude mice. Animals received 80 mg sorafenib per kilogram of body weight once daily once tumors measured 12 mm. ASL imaging was performed at baseline and day 14, with additional imaging performed for 786-0 and A498 (3 days to 12 weeks). Mean blood flow values and qualitative differences in spatial distribution of blood flow were analyzed and compared with histopathologic findings for viability and microvascular density. t Tests were used to compare differences in mean tumor blood flow. Bonferroni-adjusted P values less than .05 denoted significant differences. RESULTS: Baseline blood flow was 80.1 mL/100 g/min +/- 23.3 (standard deviation) for A498, 75.1 mL/100 g/min +/- 28.6 for 786-0, and 10.2 mL/100 g/min +/- 9.0 for Caki-1. Treated Caki-1 showed no significant change (14.9 mL/100 g/min +/- 7.6) in flow, whereas flow decreased in all treated A498 on day 14 (47.9 mL/100 g/min +/- 21.1) and in 786-0 on day 3 (20.3 mL/100 g/min +/- 8.7) (P = .003 and .03, respectively). For A498, lowest values were measured at 28-42 days of receiving sorafenib. Regions of increased flow occurred on days 35-49, 17-32 days before documented tumor growth and before significant increases in mean flow (day 77). Although 786-0 showed new, progressive regions with signal intensity detected as early as day 5 that correlated to viable tumor at histopathologic examination, no significant changes in mean flow were noted when day 3 was compared with all subsequent days (P > .99). CONCLUSION: ASL imaging provides clinically relevant information regarding tumor viability in RCC lines that respond to sorafenib. PMID- 19474377 TI - Quantitative endovascular fluorescence-based molecular imaging through blood of arterial wall inflammation. AB - PURPOSE: To evaluate an author-developed normalization algorithm for quantitative imaging of optical molecular probes through blood and to assess, in the rat aorta after focal aortic injury, the feasibility of measuring protease activity by using this method. MATERIALS AND METHODS: This study was performed according to a protocol approved by the institutional animal care committee. A Monte Carlo simulation was used to determine the pair of near-infrared (NIR) dyes that was best suited for the normalization algorithm. The authors tested the correction method in vitro and in vivo by injecting free dye mixtures intramurally in the aortas of four rats. The potential clinical utility was then evaluated by applying the method to the endovascular measurement of protease activity in a rat model of focal aortic injury. RESULTS: When the Monte Carlo simulation was used in the normalization algorithm, it was predicted that the intensities of signals from two NIR dyes would vary +/-3% across 1 mm of blood compared with the intensity of the raw fluorochrome signal, which would vary +/-60%. This result was validated in vitro. Endovascular imaging of free dye collections revealed that clinically relevant, uncontrollable differences in the amount of blood intervening between the imaging catheter and the dye collection precipitated dramatic variations in raw NIR fluorescence. However, use of the correction method resolved these variations such that the measured signal intensity correlated well with the different dye concentrations in the different animals. Moreover, endovascular imaging of the focal aortic injury model enabled successful measurement of enzyme activity in the walls of the rat aortas. CONCLUSION: The authors implemented a correction method for quantitative real time endovascular imaging of fluorescence that enables one to resolve the attenuating effects of blood on NIR signal. PMID- 19474378 TI - L-2-Hydroxyglutaric aciduria: pattern of MR imaging abnormalities in 56 patients. AB - PURPOSE: To describe the pattern of magnetic resonance (MR) imaging abnormalities in l-2-hydroxyglutaric aciduria (L2HGA) and to evaluate the correlation between imaging abnormalities and disease duration. MATERIALS AND METHODS: MR images in 56 patients (30 male, 26 female; mean age +/- standard deviation, 11.9 years +/- 8.5) with genetically confirmed L2HGA were retrospectively reviewed, with institutional review board approval and waiver of informed consent. At least one complete series of transverse T2-weighted images was available for all patients. The images were evaluated by using a previously established scoring list. The correlation between MR imaging abnormalities and disease duration was assessed (Mann-Whitney or Kruskal-Wallis test). RESULTS: The cerebral white matter (WM) abnormalities preferentially affected the frontal and subcortical regions. The abnormal subcortical WM often had a mildly swollen appearance (37 patients). Initially, the WM abnormalities were at least partially multifocal (32 patients). In patients with longer disease duration, the WM abnormalities became more confluent and spread centripetally, but the periventricular rim remained relatively spared (41 patients). The mean disease duration in patients with WM atrophy (14.8 years) was significantly longer (P = .001) than that in patients without atrophy (6.7 years). Bilateral involvement of the globus pallidus (55 patients), caudate nucleus (56 patients), and putamen (56 patients) was seen at all stages. The cerebellar WM was never affected. The dentate nucleus was involved bilaterally in 55 of 56 patients. CONCLUSION: L2HGA has a distinct highly characteristic pattern of MR imaging abnormalities: a combination of predominantly subcortical cerebral WM abnormalities and abnormalities of the dentate nucleus, globus pallidus, putamen, and caudate nucleus. With increasing disease duration, WM abnormalities and basal ganglia signal intensity abnormalities become more diffuse and cerebral WM atrophy ensues. PMID- 19474379 TI - Intracranial tumors: cisternal angle as a measure of midbrain compression for assessing risk of postembolization clinical deterioration. AB - PURPOSE: To identify objective imaging characteristics that are predictors of clinical deterioration after embolization of large intracranial tumors. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by the institutional review board, and informed consent was waived. The records of twelve patients with large intracranial tumors who underwent embolization were analyzed for imaging characteristics that would portend acute neurologic deterioration following embolization. The degree of midbrain compression was calculated by using the cisternal angle (the angle formed at the intersection of a line drawn along the midsagittal plane and a line drawn along the anterior aspect of the cerebral peduncle). Angiograms were evaluated for the degree of pre and postembolization tumor blush. Neurologic status before and after embolization was evaluated. The Wilcoxon signed rank test was used to compare the cisternal angles ipsilateral and contralateral to the tumor. The cisternal angle was measured in 100 control subjects with no mass lesions to evaluate its normal distribution. RESULTS: Of the 12 patients, three experienced acute clinical deterioration after embolization. A feature common to these patients was substantial preprocedure midbrain compression, as indicated by a cisternal angle of less than 25 degrees , which was significantly less than the mean angle in the control group. Another consistent risk factor was a strong initial tumor blush pattern and a major blush reduction following embolization. CONCLUSION: Cisternal angle is an objective measure of midbrain compression. The presence of a cisternal angle less than 25 degrees (indicating severe midbrain compression), strong tumor blush, and major postprocedure blush reduction are predictors of clinical deterioration after embolization. PMID- 19474381 TI - Case 146: Benign multicystic mesothelioma. PMID- 19474382 TI - Multidetector CT evaluation of abdominal wall for breast reconstruction: take a look at the veins. PMID- 19474383 TI - Excessive temperature increases in pacemaker leads at 3-T MR imaging with a transmit-receive head coil. PMID- 19474384 TI - Comment from the editor on Lambertz et al in the September 2008 issue. PMID- 19474385 TI - Cancer statistics, 2009. AB - Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are standardized by age to the 2000 United States standard million population. A total of 1,479,350 new cancer cases and 562,340 deaths from cancer are projected to occur in the United States in 2009. Overall cancer incidence rates decreased in the most recent time period in both men (1.8% per year from 2001 to 2005) and women (0.6% per year from 1998 to 2005), largely because of decreases in the three major cancer sites in men (lung, prostate, and colon and rectum [colorectum]) and in two major cancer sites in women (breast and colorectum). Overall cancer death rates decreased in men by 19.2% between 1990 and 2005, with decreases in lung (37%), prostate (24%), and colorectal (17%) cancer rates accounting for nearly 80% of the total decrease. Among women, overall cancer death rates between 1991 and 2005 decreased by 11.4%, with decreases in breast (37%) and colorectal (24%) cancer rates accounting for 60% of the total decrease. The reduction in the overall cancer death rates has resulted in the avoidance of about 650,000 deaths from cancer over the 15-year period. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year. Although progress has been made in reducing incidence and mortality rates and improving survival, cancer still accounts for more deaths than heart disease in persons younger than 85 years of age. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population and by supporting new discoveries in cancer prevention, early detection, and treatment. PMID- 19474386 TI - Failure of hypoxia to exaggerate the metabolic stress in working muscle following short-term training. AB - This study investigated the effects of hypoxia (experiment 1) and the effects of hypoxia following short-term training (experiment 2) on metabolism in working muscle. In experiment 1, eight males with a peak aerobic power (VO2peak) of 45 +/ 1.7 ml x kg(-1) x min(-1) (x +/- SE) cycled for 15 min at 66.1 +/- 2.1% VO2peak while breathing room air [normoxia (N)] or 14% O(2) [hypoxia (H)]. In experiment 2, nine males with a VO2peak of 43.3 +/- 1.6 ml x kg(-1) x min(-1) performed a similar protocol at 60.7 +/- 1.4% VO2peak during N and during H following 5 days of submaximal exercise training (H + T). Tissue samples extracted from the vastus lateralis before exercise and at 1, 3, and 15 min of exercise indicated that compared with N, H resulted in lower (P < 0.05) concentrations (mmol/kg dry wt) of creatine phosphate and higher (P < 0.05) concentrations of creatine, inorganic phosphate, and lactate, regardless of exercise time. When the exercise was performed at H + T and compared with N, no differences were observed in creatine phosphate, creatine, inorganic phosphate, and lactate, regardless of duration. Given the well-documented effects of the short-term training model on elevating VO2 kinetics and attenuating the alterations in high-energy phosphate metabolism and lactate accumulation, it would appear that the mechanism underlying the reversal of these adaptations during H is linked to a more rapid increase in oxidative phosphorylation, mediated by increased oxygen delivery and/or mitochondrial activation. PMID- 19474387 TI - Overexpression of follistatin in trout stimulates increased muscling. AB - Deletion or inhibition of myostatin in mammals has been demonstrated to markedly increase muscle mass by hyperplasia, hypertrophy, or a combination of both. Despite a remarkably high degree of conservation with the mammalian protein, the function of myostatin remains unknown in fish, many species of which continue muscle growth throughout the lifecycle by hyperplasia. Transgenic rainbow trout (Oncorhynchus mykiss) overexpressing follistatin, one of the more efficacious antagonists of myostatin, were produced to investigate the effect of this protein on muscle development and growth. P(1) transgenics overexpressing follistatin in muscle tissue exhibited increased epaxial and hypaxial muscling similar to that observed in double-muscled cattle and myostatin null mice. The hypaxial muscling generated a phenotype reminiscent of well-developed rectus abdominus and intercostal muscles in humans and was dubbed "six pack." Body conformation of the transgenic animals was markedly altered, as measured by condition factor, and total muscle surface area increased. The increased muscling was due almost exclusively to hyperplasia as evidenced by a higher number of fibers per unit area and increases in the percentage of smaller fibers and the number of total fibers. In several individuals, asymmetrical muscling was observed, but no changes in mobility or behavior of follistatin fish were observed. The findings indicate that overexpression of follistatin in trout, a species with indeterminate growth rate, enhances muscle growth. It remains to be determined whether the double muscling in trout is due to inhibition of myostatin, other growth factors, or both. PMID- 19474388 TI - Postprandial changes in plasma growth hormone, insulin, insulin-like growth factor (IGF)-I, and IGF-binding proteins in coho salmon fasted for varying periods. AB - We examined postprandial changes in circulating growth hormone (GH), insulin, insulin-like growth factor (IGF)-I, and IGF-binding proteins (IGFBPs) in yearling coho salmon under different feeding regimes. Fish were initially fasted for 1 day, 1 wk, or 3 wk. Fasted fish were then fed, and blood was collected at 4-h intervals over 26 h. After the various periods of fasting, basal levels of insulin were relatively constant, whereas those of IGF-I, IGFBPs and GH changed in proportion to the duration of the fast. A single meal caused a rapid, large increase in the circulating insulin levels, but the degree of the increase was influenced by the fasting period. IGF-I showed a moderate increase 2 h after the meal but only in the regularly fed fish. Plasma levels of 41-kDa IGFBP were increased in all groups within 6 h after the single meal. The fasting period did not influence the response of 41-kDa IGFBP to the meal. IGFBP-1 and GH decreased after the meal to the same extent among groups regardless of the fasting period. The present study shows that insulin and IGF-I respond differently to long (weeks)- and short (hours)-term nutritional changes in salmon; insulin maintains its basal level but changes acutely in response to food intake, whereas IGF-I adjusts its basal levels to the long-term nutritional status and is less responsive to acute nutritional input. IGFBPs maintain their sensitivity to food intake, even after prolonged fasting, suggesting their critical role in the nutritional regulation of salmon growth. PMID- 19474389 TI - Dietary sodium modulates the interaction between efferent renal sympathetic nerve activity and afferent renal nerve activity: role of endothelin. AB - Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA), which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA. We now examined whether the ERSNA-induced increases in ARNA are modulated by dietary sodium and the role of endothelin (ET). The ARNA response to reflex increases in ERSNA was enhanced in high (HNa)- vs. low-sodium (LNa) diet rats, 7,560 +/- 1,470 vs. 900 +/- 390%.s. The norepinephrine (NE) concentration required to increase PGE(2) and substance P release from isolated renal pelvises was 10 pM in HNa and 6,250 pM in LNa diet rats. In HNa diet pelvises 10 pM NE increased PGE(2) release from 67 +/- 6 to 150 +/- 13 pg/min and substance P release from 6.7 +/- 0.8 to 12.3 +/- 1.8 pg/min. In LNa diet pelvises 6,250 pM NE increased PGE(2) release from 64 +/- 5 to 129 +/- 22 pg/min and substance P release from 4.5 +/- 0.4 to 6.6 +/- 0.7 pg/min. In the renal pelvic wall, ETB-R are present on unmyelinated Schwann cells close to the afferent nerves and ETA-R on smooth muscle cells. ETA-receptor (R) protein expression in the renal pelvic wall is increased in LNa diet. In HNa diet, renal pelvic administration of the ETB-R antagonist BQ788 reduced ERSNA induced increases in ARNA and NE-induced release of PGE(2) and substance P. In LNa diet, the ETA-R antagonist BQ123 enhanced ERSNA-induced increases in ARNA and NE-induced release of substance P without altering PGE(2) release. In conclusion, activation of ETB-R and ETA-R contributes to the enhanced and suppressed interaction between ERSNA and ARNA in conditions of HNa and LNa diet, respectively, suggesting a role for ET in the renal control of ERSNA that is dependent on dietary sodium. PMID- 19474390 TI - Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. AB - Nesfatin-1 is a recently discovered hypothalamic peptide that was shown to suppress food intake through a melanocortin-3/4 receptor-dependent mechanism. Since nesfatin-1 mRNA is detected in the paraventricular nucleus of the hypothalamus, and because many peptides that alter food intake also influence cardiovascular function, we tested the ability of centrally administered nesfatin 1 to affect mean arterial pressure (MAP) in conscious, freely moving rats. Significant increases in MAP were observed following intracerebroventricular administration of nesfatin-1. Pretreatment with either the melanocortin-3/4 receptor antagonist, SHU9119 (intracerebroventricular), or the alpha-adrenergic antagonist, phentolamine (intra-arterial), abrogated the rise in MAP induced by nesfatin-1, indicating that nesfatin-1 may interact with the central melanocortin system to increase sympathetic nerve activity and lead to an increase in MAP. Thus we have identified a novel action of nesfatin-1, in addition to its anorexigenic effects, to stimulate autonomic nervous system activity. PMID- 19474391 TI - A role of the (pro)renin receptor in neuronal cell differentiation. AB - The (pro)renin receptor [(P)RR] plays a pivotal role in the renin-angiotensin system. Experimental models emphasize the role of (P)RR in organ damage associated with hypertension and diabetes. However, a mutation of the (P)RR gene, resulting in frame deletion of exon 4 [Delta4-(P)RR] is associated with X-linked mental retardation (XLMR) and epilepsy pointing to a novel role of (P)RR in brain development and cognitive function. We have studied (P)RR expression in mouse brain, as well as the effect of transfection of Delta4-(P)RR on neuronal differentiation of rat neuroendocrine PC-12 cells induced by nerve growth factor (NGF). In situ hybridization showed a wide distribution of (P)RR, including in key regions involved in the regulation of blood pressure and body fluid homeostasis. In mouse neurons, the receptor is on the plasma membrane and in synaptic vesicles, and stimulation by renin provokes ERK1/2 phosphorylation. In PC-12 cells, (P)RR localized mainly in the Golgi and in endoplasmic reticulum and redistributed to neurite projections during NGF-induced differentiation. In contrast, Delta4-(P)RR remained cytosolic and inhibited NGF-induced neuronal differentiation and ERK1/2 activation. Cotransfection of PC-12 cells with (P)RR and Delta4-(P)RR cDNA resulted in altered localization of (P)RR and inhibited (P)RR redistribution to neurite projections upon NGF stimulation. Furthermore, (P)RR dimerized with itself and with Delta4-(P)RR, suggesting that the XLMR and epilepsy phenotype resulted from a dominant-negative effect of Delta4-(P)RR, which coexists with normal transcript in affected males. In conclusion, our results show that (P)RR is expressed in mouse brain and suggest that the XLMR and epilepsy phenotype might result from a dominant-negative effect of the Delta4 (P)RR protein. PMID- 19474392 TI - Novel bUT-B2 urea transporter isoform is constitutively activated. AB - Our previous studies have detailed a novel facilitative UT-B urea transporter isoform, bUT-B2. Despite the existence of mouse and human orthologs, the functional characteristics of UT-B2 remain undefined. In this report, we produced a stable MDCK cell line that expressed bUT-B2 protein and investigated the transepithelial urea flux across cultured cell monolayers. We observed a large basal urea flux that was significantly reduced by known inhibitors of facilitative urea transporters; 1,3 dimethylurea (P < 0.001, n = 17), thionicotinamide (P < 0.05, n = 11), and phloretin (P < 0.05, n = 9). Pre exposure for 1 h to the antidiuretic hormone vasopressin had no effect on bUT-B2 mediated urea transport (NS, n = 3). Acute vasopressin exposure for up to 30 min also failed to elicit any transient response (NS, n = 9). Further investigation confirmed that bUT-B2 function was not affected by alteration of intracellular cAMP (NS, n = 4), intracellular calcium (NS, n = 3), or protein kinase activity (NS, n = 4). Finally, immunoblot data suggested a possible role for glycosylation in regulating bUT-B2 function. In conclusion, this study showed that bUT-B2 mediated transepithelial urea transport was constitutively activated and unaffected by known regulators of renal UT-A urea transporters. PMID- 19474393 TI - Retraction. PMID- 19474394 TI - Short-term memory (STM) constraints in children with specific language impairment (SLI): are there differences between receptive and expressive SLI? AB - PURPOSE: Specific language impairment (SLI) is assumed to be causally related to deficits in auditory short-term memory (STM). Although verbal STM deficits have been consistently found in SLI, the results of visual STM tests are inconsistent. Do these inconsistencies reflect different study populations of expressive SLI (ELI) and receptive-expressive SLI (R/ELI)? METHOD: Twenty-one children (ages 6 11) with ELI, 21 with R/ELI, and 21 controls (CG) matched on age and nonverbal intelligence were retrospectively compared with regard to their visual and auditory STM. RESULTS: ELI children and R/ELI children performed significantly poorer than the CG in auditory-verbal STM tests. On tests for visual STM (symbol sequences), the R/ELI children performed significantly poorer than the CG. For hand movements, children with R/ELI scored slightly poorer compared to both other groups but without reaching statistical significance. Correlation analyses showed significant associations between symbol sequences and receptive language measures. Regression analysis found that the scores of symbol sequences and digit sequences together accounted for 39% of the variance of the receptive language measures, whereas the scores for nonsense syllables accounted for 24% of the variance of the expressive language measures. CONCLUSION: R/ELI children appear to have more complex STM deficits, as they showed visual STM constraints in addition to auditory STM constraints. PMID- 19474395 TI - Syntactic frames in fast mapping verbs: effect of age, dialect, and clinical status. AB - PURPOSE: To investigate children's performance on a fast mapping task. Possible effects across age, dialect group, and clinical status were explored. METHOD: Participants between the ages of 4 and 9 saw a series of pictured events and heard novel verbs. The novel verbs were in intransitive, transitive, dative, and complement syntactic frames or argument structures. The children then had to answer questions about the novel verbs that revealed what meaning they had attached to them. The field-testing of a new assessment instrument provided the data for typically developing children and children with language impairment from 2 linguistic communities: (a) mainstream American English speaking and (b) African American English speaking. Strict criteria were used for the 529 participants that defined both their clinical and dialect status. RESULTS: There were significant effects of age and clinical status on the participants' ability to fast map a novel verb from its argument structure, but no significant effects for dialect. CONCLUSIONS: Regardless of dialect, children with specific language impairment have difficulty using syntactic frames to identify a likely meaning of a novel verb. In addition, the syntactic frames are differentially difficult, with complement structures being particularly hard. PMID- 19474396 TI - Using the self-select paradigm to delineate the nature of speech motor programming. AB - PURPOSE: The authors examined the involvement of 2 speech motor programming processes identified by S. T. Klapp (1995, 2003) during the articulation of utterances differing in syllable and sequence complexity. According to S. T. Klapp, 1 process, INT, resolves the demands of the programmed unit, whereas a second process, SEQ, oversees the serial order demands of longer sequences. METHOD: A modified reaction time paradigm was used to assess INT and SEQ demands. Specifically, syllable complexity was dependent on syllable structure, whereas sequence complexity involved either repeated or unique syllabi within an utterance. RESULTS: INT execution was slowed when articulating single syllables in the form CCCV compared to simpler CV syllables. Planning unique syllables within a multisyllabic utterance rather than repetitions of the same syllable slowed INT but not SEQ. CONCLUSIONS: The INT speech motor programming process, important for mental syllabary access, is sensitive to changes in both syllable structure and the number of unique syllables in an utterance. PMID- 19474397 TI - "You don't want to burden them": older adults' views on family involvement in care. AB - Burden emerged as an important concept among older adults in a study of how older adults interact with their families around care. The authors conducted 50 semistructured interviews with adults older than the age of 65 years and a spouse or adult child. The sample was stratified by ethnicity thus giving the opportunity to explore both ethnic similarities and differences. Older adults who expressed the concept of burden were more likely to be White compared with older adults who did not express burden. Older respondents discussed burden in relation to not wanting to complicate the busy lives of adult children, guilt about health problems, and concern that children were overly worried about the care of their older family member. The expression and meaning of burden differed according to ethnicity. This study has implications for practice and policies to meet the needs of families and promote the independence of older persons. PMID- 19474398 TI - Twenty-four hour ocular perfusion pressure fluctuation and risk of normal-tension glaucoma progression. AB - PURPOSE: To investigate the relationship between clinical factors including 24 hour mean ocular perfusion pressure (MOPP, (2/3) x mean arterial pressure [MAP] - intraocular pressure [IOP]) and visual field (VF) progression in eyes with medically treated normal-tension glaucoma (NTG). METHODS: One hundred one eyes of 101 NTG patients followed up for more than 4 years (mean follow-up, 6.2 years +/- 12.1 months) were included after retrospective chart review. Several clinical factors including demographic, systemic, ocular risk factors, and 24-hour MOPP were explored for associations with decreasing VF. Kaplan-Meier analyses were performed to compare outcomes with reference to four risk factors (age, myopia, and elevated MAP and MOPP fluctuation) for VF deterioration. Hazard ratios (HRs) for the association between potential risk factors and glaucoma progression were obtained using Cox proportional hazards models. RESULTS: Overall VF progression was detected in 29 (28.7%) eyes. There were significant differences between progressors and nonprogressors in nocturnal MAP and MOPP fluctuations (both P < 0.0001), 24-hour MAP, and MOPP fluctuations (both P < 0.0001), initial mean deviation (P = 0.0034), and pattern standard deviation (PSD) score (P < 0.0001). Both elevated 24-hour MAP and MOPP fluctuations were associated with greater VF progression probabilities based on Kaplan-Meier analyses. Among all risk factors investigated, the Cox proportional hazards model indicated that VF progression was significantly associated with 24-hour MOPP fluctuation and initial PSD score. CONCLUSIONS: Clinical factors other than IOP were associated with VF progression in our series of medically treated NTG eyes. Twenty-four-hour MOPP fluctuation was the most consistent prognostic factor for glaucoma progression. PMID- 19474400 TI - The mydriatic effect of intracameral epinine hydrochloride. AB - PURPOSE: To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model. METHODS: One hundred twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg intracameral acetylcholine to give miosis, 0.15 mL epinine or phenylephrine 0.3%, 1.5%, or 3.0% was given as an intracameral injection. The pupils were filmed during 90 seconds with a video camera connected to an operation microscope, and the mean pupil diameters were measured from the video recordings. In 37 additional eyes, 0.15 mL vehicle, 1.5% epinine, or 1.5% phenylephrine was injected intracamerally, and the eyes were kept on ice overnight. Corneal endothelial morphology was assessed before and after the treatment. Ten eyes were given no injection and served as controls. RESULTS; Epinine had a significantly larger mydriatic effect than phenylephrine at equal concentrations. Endothelial cell loss was equal with both substances and did not exceed that of the vehicle. CONCLUSIONS: Epinine was a more potent mydriatic than phenylephrine in this porcine eye model. The porcine eye model appears suitable as a first efficacy screening of substances for intraocular use. Epinine is a promising candidate substance for intraoperative (e.g., cataract surgery) intracameral use in humans. PMID- 19474399 TI - Null retinoschisin-protein expression from an RS1 c354del1-ins18 mutation causing progressive and severe XLRS in a cross-sectional family study. AB - PURPOSE: To explore the retinoschisin (RS1) protein biochemical phenotype from an RS1 exon-5 deletion/insertion frame-shift mutation in a family with X-linked retinoschisis (XLRS) and describe the clinical and electrophysiological features. METHODS: Six XLRS males underwent ophthalmic examination and electroretinogram (ERG) recording. The RS1 gene was sequenced. Mutant RS1-RNA and protein expression were assessed by transfecting COS-7 cells with minigene constructs. RESULTS: All six males carried the RS1 c354del1-ins18 mutation in which an 18-bp insertion replaced nucleotide 354, duplicating the adjacent upstream intron 4-to exon 5 junction and creating a premature termination codon downstream. Analysis indicated normal pre-mRNA splicing producing mRNA transcripts. Truncated RS1 protein was expressed transiently but was degraded rapidly by a proteasomal pathway rather than by nonsense-mediated mRNA decay. Two boys, 1.5 and 5 years of age, had foveal cysts and minimal peripheral schisis, and retained near-normal scotopic b-wave amplitude and normal ERG waveforms. The 5-year-old's ERG was diminished when repeated 3 years later. Four older XLRS relatives 32 to 45 years old had substantial b-wave loss and strongly electronegative ERGs; three had overt macular atrophy. Cross-sectional family analysis showed the b-/a-wave amplitude ratio as inversely related to age in the six males. CONCLUSIONS: The c354del1-ins18 mutation caused an RS1-null biochemical phenotype and a progressive clinical phenotype in a 5-year-old boy, whereas the older XLRS relatives had macular atrophy and marked ERG changes. The phenotypic heterogeneity with age by cross-sectional study of this family mutation argues that XLRS disease is not stationary and raises questions regarding factors involved in progression. PMID- 19474401 TI - Disruption of zonula occludens-1 localization in the rabbit corneal epithelium by contact lens-induced hypoxia. AB - PURPOSE: Hypoxia impairs the barrier function of the corneal epithelium. This function depends on tight junctions, of which zonula occludens (ZO)-1 is a major component. The authors have investigated the effects of hypoxia on ZO-1 localization and expression in the rabbit corneal epithelium in vivo. METHODS: A polymethylmethacrylate (PMMA) or rigid gas-permeable (RGP) lens was applied to one eye each of albino rabbits for 24 hours. The structure of the corneal epithelium was examined by in vivo confocal microscopy, and epithelial barrier function was evaluated by measurement of central corneal thickness. The distribution and expression of ZO-1 in the corneal epithelium were examined by immunofluorescence analysis and by immunoblot and reverse transcription polymerase chain reaction analyses, respectively. RESULTS: Application of a PMMA lens, but not that of an RGP lens, resulted in a reduction in cell size at the surface of the corneal epithelium, compared with that in control eyes, and an increase in central corneal thickness. Immunofluorescence analysis revealed a continuous pattern of ZO-1 immunoreactivity around the perimeter of superficial corneal epithelial cells in control eyes or in eyes treated with an RGP lens. In contrast, the pattern of ZO-1 staining was discontinuous and patchy in eyes treated with a PMMA lens. Amounts of ZO-1 mRNA and protein in the corneal epithelium were reduced by application of a PMMA lens but not by that of an RGP lens. CONCLUSIONS: Hypoxia at the ocular surface induced the disruption of tight junctions between superficial cells in the rabbit corneal epithelium in vivo. PMID- 19474403 TI - More irregular eye shape in low myopia than in emmetropia. AB - PURPOSE: To improve the description of the peripheral eye shape in myopia and emmetropia by using a new method for continuous measurement of the peripheral refractive state. METHODS: A scanning photorefractor was designed to record refractive errors in the vertical pupil meridian across the horizontal visual field (up to +/-45 degrees ). The setup consists of a hot mirror that continuously projects the infrared light from a photoretinoscope under different angles of eccentricity into the eye. The movement of the mirror is controlled by using two stepping motors. Refraction in a group of 17 emmetropic subjects and 11 myopic subjects (mean, -4.3 D; SD, 1.7) was measured without spectacle correction. For the analysis of eye shape, the refractive error versus the eccentricity angles was fitted with different polynomials (from second to tenth order). RESULTS: The new setup presents some important advantages over previous techniques: The subject does not have to change gaze during the measurements, and a continuous profile is obtained rather than discrete points. There was a significant difference in the fitting errors between the subjects with myopia and those with emmetropia. Tenth-order polynomials were required in myopic subjects to achieve a quality of fit similar to that in emmetropic subjects fitted with only sixth-order polynomials. Apparently, the peripheral shape of the myopic eye is more "bumpy." CONCLUSIONS: A new setup is presented for obtaining continuous peripheral refraction profiles. It was found that the peripheral retinal shape is more irregular even in only moderately myopic eyes, perhaps because the sclera lost some rigidity even at the early stage of myopia. PMID- 19474402 TI - Retinal endothelial cell apoptosis stimulates recruitment of endothelial progenitor cells. AB - PURPOSE: Bone marrow-derived endothelial progenitor cells (EPCs) contribute to vascular repair although it is uncertain how local endothelial cell apoptosis influences their reparative function. This study was conducted to determine how the presence of apoptotic bodies at sites of endothelial damage may influence participation of EPCs in retinal microvascular repair. METHODS: Microlesions of apoptotic cell death were created in monolayers of retinal microvascular endothelial cells (RMECs) by using the photodynamic drug verteporfin. The adhesion of early-EPCs to these lesions was studied before detachment of the apoptotic cells or after their removal from the wound site. Apoptotic bodies were fed to normal RMECs and mRNA levels for adhesion molecules were analyzed. RESULTS: Endothelial lesions where apoptotic bodies were left attached at the wound site showed a fivefold enhancement in EPC recruitment (P < 0.05) compared with lesions where the apoptotic cells had been removed. In intact RMEC monolayers exposed to apoptotic bodies, expression of ICAM, VCAM, and E-selectin was upregulated by 5- to 15-fold (P < 0.05-0.001). EPCs showed a characteristic chemotactic response (P < 0.05) to conditioned medium obtained from apoptotic bodies, whereas analysis of the medium showed significantly increased levels of VEGF, IL-8, IL-6, and TNF-alpha when compared to control medium; SDF-1 remained unchanged. CONCLUSIONS: The data indicate that apoptotic bodies derived from retinal capillary endothelium mediate release of proangiogenic cytokines and chemokines and induce adhesion molecule expression in a manner that facilitates EPC recruitment. PMID- 19474404 TI - Cellular and vascular changes in the retina of neonatal rats after an acute exposure to hypoxia. AB - PURPOSE: This study was undertaken to examine the effects of an acute hypoxic exposure on the retinal cells and production of vascular factors such as vascular endothelial growth factor (VEGF) and nitric oxide (NO), which may affect vascular permeability in the developing retina. METHODS: Retinas of 1-day-old rats were examined at 3 hours to 14 days after hypoxic exposure. The mRNA and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha), VEGF, endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), and inducible NOS (iNOS) were determined by real-time RT-PCR, Western blot analysis, and immunohistochemistry. Electron microscopy was used to examine the structural alterations in retinal cells, and rhodamine isothiocyanate (RhIC) or horseradish peroxidase (HRP) was administered intraperitoneally or intravenously to determine vascular permeability. RESULTS: The mRNA and protein expression of HIF-1alpha, VEGF, eNOS, nNOS, and iNOS, along with VEGF concentration and NO production, were increased in response to hypoxia. Swollen Muller cell processes, apoptotic and necrotic cells in the inner nuclear layer, and changes in ganglion cells such as swollen and disrupted mitochondria were observed in hypoxic animals. Increased leakage of RhIC and HRP from retinal and hyaloid vessels was seen after hypoxic exposure. CONCLUSIONS: The authors suggest that increased VEGF and NO production in hypoxia resulted in increased vascular permeability, leading to changes in Muller cells and degeneration of neural cells. Melatonin administration reduced VEGF and NO production, diminished leakage of RhIC and HRP, and promoted cell proliferation, suggesting this as a potential therapeutic agent in reducing hypoxia-associated damage in the developing retina. PMID- 19474405 TI - Secondary retinal ganglion cell death and the neuroprotective effects of the calcium channel blocker lomerizine. AB - PURPOSE: After partial optic nerve (ON) injury, intact retinal ganglion cells (RGCs) undergo secondary death, but the topographic distribution of this death is unknown, and it is unclear which cell death pathways are involved. Although the calcium channel blocker lomerizine reduces RGC death after partial ON injury, it is unknown whether this drug alleviates necrotic or apoptotic death. METHODS: The dorsal ON was transected in adult Piebald-Virol-Glaxo (PVG) rats, and the site of secondary RGC death was determined using anterograde and retrograde DiI tracing. RGC death was assessed at 2 and 3 weeks. Retrograde tracing with fluorogold injected into the superior colliculus 3 days before euthanatization was used to identify RGCs undergoing secondary death. Overall cell loss was quantified using betaIII-tubulin immunohistochemistry. Lomerizine (30 mg/kg, oral) or vehicle was given twice daily, and retinal wholemounts were analyzed for necrotic morphology (nucleic acid stain) or anticleaved caspase-3 expression at 2 and 3 weeks. RESULTS: Ventral retina was identified as the site of secondary RGC death, and central and dorsal retinae were defined as sites of both primary and secondary death. Overall RGC loss occurred by 2 weeks in central and ventral retina (P < 0.05) and by 3 weeks in dorsal retina (P < 0.05). Secondary RGC death was characterized mainly by necrotic morphology, with caspase-3 expression in some RGCs. Lomerizine reduced secondary necrosis at 2 weeks and secondary caspase-3 expression at 3 weeks. CONCLUSIONS: Lomerizine had differential effects on necrotic and apoptotic death with time, but its inability to completely prevent secondary death suggests that full neuroprotection will require combinatorial treatments. PMID- 19474406 TI - Strain-dependent increases in retinal inflammatory proteins and photoreceptor FGF 2 expression in streptozotocin-induced diabetic rats. AB - PURPOSE: Inflammation is thought to play a role in disease progression and vision loss in diabetic retinopathy (DR). However, the level of inflammation and the role of cytokines and growth factors in the early stages of this disease are poorly understood. Streptozotocin (STZ)-induced hyperglycemia in rats is widely used as a model of diabetic retinopathy, and therefore this model was used to better define the inflammatory response and the impact of the genetic background. METHODS: The expression of a panel of 57 inflammatory proteins and growth factors in the retina of three rat strains was compared by using a highly sensitive flow cytometry-based assay. Hyperglycemia was induced in Brown Norway (BN), Long-Evans (LE), and Sprague-Dawley (SD) rats, and protein expression in the retina was measured 4 weeks and 3 months later. RESULTS: The data revealed a subtle, but reproducible, inflammatory response in the retina of SD, but not in those of BN or LE, rats. Upregulation of fibroblast growth factor (FGF)-2 in the photoreceptor nuclear layer coincided with the inflammatory response in SD rats and may constitute a neuroprotective mechanism. Reduced expression of genes involved in the phototransduction pathway indicates altered photoreceptor function. CONCLUSIONS: Taken together, these data show that inflammatory changes in the diabetic rat retina are highly strain dependent, and SD rats exhibit low level inflammation similar to that observed in diabetic patients. Therefore, SD rats may be a good model for the study of early inflammatory changes in human diabetic retinopathy. PMID- 19474407 TI - Intravitreal infliximab clearance in a rabbit model: different sampling methods and assay techniques. AB - PURPOSE: To investigate the clearance of intravitreal infliximab with the use of different sampling techniques and immunoassay methods in rabbits. METHODS: Infliximab (1.6 mg) was intravitreally injected into both eyes of 47 rabbits. Two approaches were used to collect the vitreous: the classic method and a microsampling technique. Whereas the classic method consists of collection of the whole vitreous after enucleation, the microsampling technique consisted of the aspiration of small (10-15 microL) samples with a 200-microL syringe. Samples were taken from 30 minutes to 40 days using both methods and were then compared. Infliximab concentration was estimated with competitive ELISA, dot blot analysis, and Western blot analysis. RESULTS: The vitreous half-life of infliximab was estimated to be 6.5 +/- 0.6 days. The data indicated monoexponential decay reaching its conclusion after approximately 40 days. This decay was preceded by 4 day-long diffusion in the vitreous. Microsampling proved to be effective in the vitreous collection, giving statistically comparable signals (+/- 4%, P = 0.68) with respect to the classic procedure. ELISA proved to be the best analytical technique--especially if coupled with microsamplings--because of its lower detection limit, precision, and reduced amount of sample needed. No differences were observed between half-life values obtained by ELISA and dot blot analysis (P = 0.081) and Western blot analysis (P = 0.614). CONCLUSIONS: The findings of this study added to the knowledge of infliximab clearance in the vitreous and confirmed the validity of a microsampling technique that was compared with the classic one. ELISA was found to be the best analytical technique when using microsampling. PMID- 19474409 TI - Optic disc and visual field changes after trabeculectomy. AB - PURPOSE: To assess the changes in optic nerve head (ONH) structure and visual field (VF) sensitivity over time in a cohort of patients with glaucoma after trabeculectomy. METHODS: The MoreFlow Medical Research Council 5-Fluorouracil (5 FU) study was an 80-month prospective randomized controlled trial of per operative 5-FU versus placebo on the outcomes of primary trabeculectomy. Before surgery, patients had ONH imaging with a retinal tomograph and full-threshold visual field testing. After surgery, ONH imaging was performed annually and VF testing at 4-month intervals. This analysis included only patients with a minimum of 3 years' postoperative ONH and VF data. ONH images were analyzed by linear regression of sector rim area (RA) over time with change defined as a significant slope >1% of baseline RA per year in any sector. VFs were analyzed with point wise linear regression analysis (PLRA) techniques with the stringent three omitting criteria used. Eyes were classed as progressing or not based on analysis with either technique. Patients' median IOP level, intervisit IOP fluctuation, and percentage reduction in IOP over the follow-up period were also determined. RESULTS: Two hundred fifty eyes of 250 patients were suitable for analysis. Of these, 70 (28%) eyes were deemed to show glaucoma progression approximately 5 years after surgery: 20 eyes by ONH alone, 35 by VF alone, and 15 by both methods. Of the 15 shown to be progressing by both ONH and VF analysis, only 7 (3% total cohort) showed congruity in the location of change. Eyes showing changes in both ONH and VF sensitivity had slightly higher median follow-up IOP (median IOP [interquartile range; IQR] nonprogressors 14.0 mm Hg [11.8-16.0 mm Hg], progressors 15.1 mm Hg [12.7-17.0 mm Hg]; Mann-Whitney U test [MWU]; P = 0.03) and lower degrees of IOP reduction from baseline (percentage IOP reduction [IQR]: nonprogressors -38.4% [-51.8% to -26.4%]; progressors -31.4% [-43.1% to 21.5%]; MWU P = 0.01) compared with eyes showing no progression. CONCLUSIONS: The study demonstrates that approximately one third of eyes continued to show progression of glaucoma at five years after trabeculectomy, as determined by trend-based analysis of ONH structural changes and VF sensitivity over time. The study suggests that the degree of IOP reduction after trabeculectomy may play an important role in the progression of glaucoma as detected by both functional and structural methods. PMID- 19474408 TI - Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery. AB - PURPOSE: Filtration failure due to excessive postoperative scarring remains a major problem after glaucoma surgery. The authors have investigated whether glaucoma and filtration surgery are associated with increased levels of vascular endothelial growth factor (VEGF), and whether a humanized monoclonal antibody against VEGF, bevacizumab, can reduce postoperative scar formation and improve surgical outcome. METHODS: The levels of VEGF in samples of aqueous humor were measured by ELISA. The expression of the VEGF receptors Flt-1 and KDR was analyzed in cultured Tenon fibroblasts by real-time RT-PCR and Western blotting. The effect of VEGF and bevacizumab on Tenon fibroblasts in vitro was determined using a proliferation assay. The in vivo effect of the antibody was investigated in a rabbit model of trabeculectomy by measuring the intraocular pressure (IOP) and bleb area, and by immunohistological analysis of angiogenesis, inflammation, and fibrosis. RESULTS: VEGF levels were increased significantly in the aqueous humor of glaucoma patients and rabbits that had undergone surgery. Both VEGF receptors were expressed on Tenon fibroblasts. Fibroblast proliferation in vitro was stimulated by delivery of VEGF, and was inhibited by administration of bevacizumab. The antibody also reduced angiogenesis and collagen deposition significantly, and improved the outcome of glaucoma surgery in rabbits. CONCLUSIONS: VEGF was upregulated in the aqueous humor of glaucoma patients and in the rabbit model, and it stimulated fibroblast proliferation in vitro. This suggests that it is involved in the scarring process after filtration surgery. Bevacizumab reduced the proliferation of fibroblasts in vitro and improved surgical outcome. PMID- 19474410 TI - Retrograde intraflagellar transport by cytoplasmic dynein-2 is required for outer segment extension in vertebrate photoreceptors but not arrestin translocation. AB - PURPOSE: Anterograde intraflagellar transport (IFT) is essential for photoreceptor outer segment formation and maintenance, as well as for opsin trafficking. However, the role of retrograde IFT in vertebrate photoreceptors remains unclear. The purpose of this study was to evaluate zebrafish photoreceptors lacking the retrograde IFT motor, cytoplasmic dynein-2. METHODS: Morpholino oligonucleotides against the heavy chain (dync2-h1), light intermediate chain (dync2-li1), and intermediate chain (dync2-i1) subunits of cytoplasmic dynein-2 were injected into zebrafish embryos. Retinas and ciliated cells of these zebrafish morphants were analyzed by immunohistochemistry and transmission electron microscopy. Whole-field electroretinograms (ERGs) were performed on dynein morphants at 5 to 6 days after fertilization (dpf). RESULTS: Zebrafish lacking cytoplasmic dynein-2 function exhibited small eyes, kidney cysts, and short photoreceptor outer segments, some of which were disorganized with accumulated vesicles. Morphant photoreceptor connecting cilia were swollen, but neither opsin nor arrestin was mislocalized, although IFT88 accumulated in the distal region of the connecting cilium. Nasal cilia were shortened and displayed cytoplasmic swelling along the axoneme. Loss of cytoplasmic dynein-2 function resulted in a significant reduction in the amplitude of ERG a-, b-, and d-waves but no change in threshold response. CONCLUSIONS: Retrograde IFT is essential for outer segment extension and IFT protein recycling in vertebrate photoreceptors. The results show, for the first time, that the dync2-i1 subunit of cytoplasmic dynein-2 is necessary for retrograde IFT. In addition, arrestin translocation does not require retrograde IFT. Finally, the ERG results indicate that loss of cytoplasmic dynein-2 reduces the photoreceptor light response. PMID- 19474411 TI - Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET. AB - OBJECTIVE: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). METHODS: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C] methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. RESULTS: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. CONCLUSIONS: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies. PMID- 19474412 TI - Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. AB - OBJECTIVE: To rigorously evaluate the time course of cognitive change in a cohort of individuals with HIV-associated neurocognitive disorders (HAND) initiating combination antiretroviral therapy (CART), and to investigate which demographic, laboratory, and treatment factors are associated with neuropsychological (NP) outcome (or "any NP improvement"). METHODS: Study participants included 37 HIV+ individuals with mild to moderate NP impairment who initiated CART and underwent NP testing at 12, 24, 36, and 48 weeks thereafter. NP change was assessed using a regression-based change score that was normed on a separate NP-stable group thereby controlling for regression toward the mean and practice effect. Mixed effect regression models adjusting for loss to follow-up were used to evaluate the time course of cognitive change and its association with baseline and time varying predictors. RESULTS: In persons with HAND initiating CART, cognitive improvement happens soon after initiation (13% at week 12), but more often 24, 36, and up to 48 weeks after initiation (up to 41%), with fewer than 5% demonstrating significant worsening. In multivariate analyses, unique predictors of NP improvement included more severe baseline NP impairment and higher CART CNS penetration index. Greater viral load decrease was associated with NP improvement only in univariate analyses. CONCLUSION: Clinically meaningful neuropsychological improvement seemed to peak around 24-36 weeks after combination antiretroviral therapy initiation and was prolonged over the 1-year study period. This study also provides new evidence that benefit may be maximized by choosing antiretroviral medications that reach therapeutic concentrations in the CNS. PMID- 19474414 TI - I like to jump on my trampoline: an analysis of drawings from 8- to 12-year-old children beginning a weight-management program. AB - The main objective of this exploratory study was to assess children's perceptions of their activity choices as they began a weight-management program for overweight children and their families. During pretesting of a 10-week weight management program, participating children were asked to draw pictures of themselves doing something. The drawings of 35 children, ages 8 to 12, were qualitatively analyzed. The analysis focused on (a) the type of activities (i.e., physical or sedentary) children chose to convey, (b) the specific focus of the activities described, (c) the children's future activity choices, and (d) the children's responses to the activities they drew. Seventy-one percent of the participating children drew themselves engaged in a physical activity. These results are notable and suggest positive perceptions of physical activities. Children's views related to their activity choices might play a role in designing weight-management programs that successfully increase children's adherence to long-term physical activity. PMID- 19474413 TI - Obesity is a common comorbidity for pediatric patients with untreated, newly diagnosed epilepsy. AB - OBJECTIVE: This study aimed to determine the frequency and factors associated with obesity in a cohort of children and adolescents with newly diagnosed untreated epilepsy. METHODS: Body mass index (BMI) Z-scores and percentiles, both adjusted for age, were used as measures for obesity. Potential covariates associated with these BMI measures included age, etiology (cryptogenic, idiopathic, symptomatic), seizure type (generalized, partial, unclear), concomitant medications (stimulants, nonstimulants, none), and insurance status (privately insured, Medicaid). The primary analysis compared the epilepsy patients' BMI Z-scores to Centers for Disease Control and Prevention data for healthy children. The secondary analysis compared the epilepsy patients' BMI Z scores to those of a regional healthy control group. Additional analyses incorporated the secondary outcome measure BMI percentiles indexed for age. RESULTS: Children with newly diagnosed untreated epilepsy had higher BMI Z-scores compared to standard CDC growth charts (p < 0.0001) and the healthy control cohort (p = 0.0002) specifically at both of the 2 tail ends of the distribution. Overall, 38.6% of the epilepsy cohort were overweight or obese (BMI > or =85th percentile for age). Differences in age, etiology, and concomitant nonepilepsy medications were significantly associated with variability in age-adjusted BMI Z score. Patients in adolescence had higher adjusted BMI Z-scores than younger patients. Patients with symptomatic epilepsy had lower adjusted BMI Z-scores than patients with idiopathic epilepsy. Patients on stimulant psychotropics exhibited lower adjusted BMI Z-scores than patients on no medication. CONCLUSION: Obesity is a common comorbidity in children with newly diagnosed untreated epilepsy and correlates with increasing age, idiopathic etiology, and absence of concomitant medication. PMID- 19474415 TI - Communication channels in general internal medicine: a description of baseline patterns for improved interprofessional collaboration. AB - General internal medicine (GIM) is a communicatively complex specialty because of its diverse patient population and the number and diversity of health care providers working on a medicine ward. Effective interprofessional communication in such information-intensive environments is critical to achieving optimal patient care. Few empirical studies have explored the ways in which health professionals exchange patient information and the implications of their chosen communication forms. In this article, we report on an ethnographic study of health professionals' communication in two GIM wards through the lens of communication genre theory. We categorize and explore communication in GIM into two genre sets-synchronous and asynchronous-and analyze the relationship between them. Our findings reveal an essential relationship between synchronous and asynchronous modes of communication that has implications for the effectiveness of interprofessional collaboration in this and similar health care settings, and is intended to inform efforts to overcome existing interprofessional communication barriers. PMID- 19474416 TI - Spontaneous aortitis in the Balb/c mouse. AB - We examined whether high incidence rates (18%-56%) of inflammation in the root of the aorta detected in a Balb/c mouse model for hind limb ischemia were related to the surgical procedure. Twenty mice underwent ligation of the femoral artery; incidences of aortic root inflammation were compared to those observed in controls. We used a multiple-section sampling method to increase the sensitivity of the diagnostic rates. Although a cumulative incidence of 12.5% was found, no difference was seen in the overall incidence rates between the control and the surgically treated groups. Evaluation of blood levels of inflammatory cytokines showed that ligation of the femoral artery produced higher levels of interleukin 6 in the surgically transected group of mice. The development of spontaneous arteritis in this strain must be considered in future studies. PMID- 19474417 TI - Managing and reducing uncertainty in an emerging influenza pandemic. PMID- 19474418 TI - Geographic dependence, surveillance, and origins of the 2009 influenza A (H1N1) virus. PMID- 19474419 TI - CMS's landmark decision on CT colonography--examining the relevant data. PMID- 19474420 TI - Left atrial appendage occlusion--closure or just the beginning? PMID- 19474421 TI - Images in clinical medicine. Tongue necrosis in a patient with essential thrombocytosis. PMID- 19474422 TI - Healthy competition--the why and how of "public-plan choice". PMID- 19474423 TI - Public health care and health insurance reform--varied preferences, varied options. PMID- 19474424 TI - The proposed government health insurance company--no substitute for real reform. PMID- 19474425 TI - Radiofrequency ablation in Barrett's esophagus with dysplasia. AB - BACKGROUND: Barrett's esophagus, a condition of intestinal metaplasia of the esophagus, is associated with an increased risk of esophageal adenocarcinoma. We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett's esophagus and decrease the rate of neoplastic progression. METHODS: In a multicenter, sham-controlled trial, we randomly assigned 127 patients with dysplastic Barrett's esophagus in a 2:1 ratio to receive either radiofrequency ablation (ablation group) or a sham procedure (control group). Randomization was stratified according to the grade of dysplasia and the length of Barrett's esophagus. Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia. RESULTS: In the intention-to-treat analyses, among patients with low-grade dysplasia, complete eradication of dysplasia occurred in 90.5% of those in the ablation group, as compared with 22.7% of those in the control group (P<0.001). Among patients with high-grade dysplasia, complete eradication occurred in 81.0% of those in the ablation group, as compared with 19.0% of those in the control group (P<0.001). Overall, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, as compared with 2.3% of those in the control group (P<0.001). Patients in the ablation group had less disease progression (3.6% vs. 16.3%, P=0.03) and fewer cancers (1.2% vs. 9.3%, P=0.045). Patients reported having more chest pain after the ablation procedure than after the sham procedure. In the ablation group, one patient had upper gastrointestinal hemorrhage, and five patients (6.0%) had esophageal stricture. CONCLUSIONS: In patients with dysplastic Barrett's esophagus, radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression. (ClinicalTrials.gov number, NCT00282672.) PMID- 19474426 TI - Mutation in TET2 in myeloid cancers. AB - BACKGROUND: The myelodysplastic syndromes and myeloproliferative disorders are associated with deregulated production of myeloid cells. The mechanisms underlying these disorders are not well defined. METHODS: We conducted a combination of molecular, cytogenetic, comparative-genomic-hybridization, and single-nucleotide-polymorphism analyses to identify a candidate tumor-suppressor gene common to patients with myelodysplastic syndromes, myeloproliferative disorders, and acute myeloid leukemia (AML). The coding sequence of this gene, TET2, was determined in 320 patients. We analyzed the consequences of deletions or mutations in TET2 with the use of in vitro clonal assays and transplantation of human tumor cells into mice. RESULTS: We initially identified deletions or mutations in TET2 in three patients with myelodysplastic syndromes, in three of five patients with myeloproliferative disorders, in two patients with primary AML, and in one patient with secondary AML. We selected the six patients with myelodysplastic syndromes or AML because they carried acquired rearrangements on chromosome 4q24; we selected the five patients with myeloproliferative disorders because they carried a dominant clone in hematopoietic progenitor cells that was positive for the V617F mutation in the Janus kinase 2 (JAK2) gene. TET2 defects were observed in 15 of 81 patients with myelodysplastic syndromes (19%), in 24 of 198 patients with myeloproliferative disorders (12%) (with or without the JAK2 V617F mutation), in 5 of 21 patients with secondary AML (24%), and in 2 of 9 patients with chronic myelomonocytic leukemia (22%). TET2 defects were present in hematopoietic stem cells and preceded the JAK2 V617F mutation in the five samples from patients with myeloproliferative disorders that we analyzed. CONCLUSIONS: Somatic mutations in TET2 occur in about 15% of patients with various myeloid cancers. PMID- 19474427 TI - Age, neuropathology, and dementia. AB - BACKGROUND: Research in Alzheimer's disease is focused mainly on younger old persons, whereas studies involving very old persons report attenuated relationships between the pathological features of Alzheimer's disease and dementia. METHODS: We assessed 456 brains donated to the population-based Medical Research Council Cognitive Function and Ageing Study from persons 69 to 103 years of age at death. We used a standard neuropathological protocol that included measures of the pathological features of Alzheimer's disease, cerebral atrophy, and cerebrovascular disease. Neuropathological variables were dichotomized to represent no burden or a mild burden of pathological lesions as compared with a moderate or severe burden. Logistic regression was used to estimate the effect of age on the relationship between neuropathological features and dementia. RESULTS: The difference in the prevalence of moderate and severe Alzheimer's-type pathological changes between persons with and those without dementia decreased with increasing age. The association between neocortical neuritic plaques and dementia was strong at 75 years of age (odds ratio, 8.63; 95% confidence interval [CI], 3.81 to 19.60) and reduced at 95 years of age (odds ratio, 2.48; 95% CI, 0.92 to 4.14), and similar attenuations with advancing age were observed in the association between other pathological changes related to Alzheimer's disease and dementia in all brain areas. In contrast, neocortical cerebral atrophy maintained a relationship with age in persons with dementia at both 75 years of age (odds ratio, 5.11; 95% CI, 1.94 to 13.46) and 95 years of age (odds ratio, 6.10; 95% CI, 2.80 to 13.28) and thus distinguished the cohort with dementia from the cohort without dementia. CONCLUSIONS: The association between the pathological features of Alzheimer's disease and dementia is stronger in younger old persons than in older old persons. Age must be taken into account when assessing the likely effect of interventions against dementia on the population. PMID- 19474428 TI - Inactivating PAPSS2 mutations in a patient with premature pubarche. AB - Dehydroepiandrosterone (DHEA) sulfotransferase, known as SULT2A1, converts the androgen precursor DHEA to its inactive sulfate ester, DHEAS [corrected], thereby preventing the conversion of DHEA to an active androgen. SULT2A1 requires 3' phosphoadenosine-5'-phosphosulfate (PAPS) for catalytic activity. We have identified compound heterozygous mutations in the gene encoding human PAPS synthase 2 (PAPSS2) in a girl with premature pubarche, hyperandrogenic anovulation, very low DHEAS levels, and increased androgen levels. In vitro coincubation of human SULT2A1 and wild-type or mutant PAPSS2 proteins confirmed the inactivating nature of the mutations. These observations indicate that PAPSS2 deficiency is a monogenic adrenocortical cause of androgen excess. PMID- 19474429 TI - Clinical practice. Chronic venous insufficiency and varicose veins. PMID- 19474430 TI - Predisposing factors for adrenal insufficiency. PMID- 19474431 TI - Images in clinical medicine. Pharyngeal mass in a patient with B-cell lymphoma. PMID- 19474432 TI - Case records of the Massachusetts General Hospital. Case 17-2009. A 30-year-old man with progressive neurologic deficits. PMID- 19474433 TI - Radiofrequency ablation--great for some or justified for many? PMID- 19474434 TI - A common genetic mechanism in malignant bone marrow diseases. PMID- 19474435 TI - Cool with plaques and tangles. PMID- 19474436 TI - Handguns, health, and the Second Amendment. PMID- 19474437 TI - Breast cancer and hormonal therapy in postmenopausal women. PMID- 19474438 TI - Endocrine therapy plus zoledronic acid in premenopausal breast cancer. PMID- 19474439 TI - Long-term consequences of kidney donation. PMID- 19474440 TI - A surgical safety checklist. PMID- 19474441 TI - Asthma induced by a thermal printer. PMID- 19474442 TI - The AAOS clinical practice guidelines. PMID- 19474443 TI - Anterior iliopsoas impingement and tendinitis after total hip arthroplasty. AB - Anterior iliopsoas impingement and tendinitis is a poorly understood and likely underrecognized cause of groin pain and functional disability after total hip arthroplasty. The patient history and physical examination findings are usually only suggestive, and the symptoms frequently subtle. The diagnosis may be confirmed by one or more imaging studies, including a cross-table lateral radiograph, computed tomography, magnetic resonance imaging, and ultrasonography, in combination with a confirmatory diagnostic injection. Nonsurgical management may not resolve the problem. Surgical treatment, consisting of release or resection of the iliopsoas tendon, alone or in combination with acetabular revision for an anterior overhanging component, usually provides permanent pain relief. PMID- 19474444 TI - Osteonecrosis of the humeral head. AB - Osteonecrosis of the humeral head is considerably less common than osteonecrosis of the hip. However, as in the hip, the interaction between a genetic predisposition and certain risk factors may lead to increased intraosseous pressure, loss of circulation, and eventual bone death. The most common risk factor remains corticosteroid use, which accounts for most reported cases. Radiographic staging and measurement of lesion size are predictive of disease progression and can be used to determine appropriate intervention. Recent studies have reported the use of various treatment modalities such as pharmacologics, core decompression with small-diameter drilling, arthroscopic-assisted core decompression, and bone grafting. Prospective, randomized studies are needed to determine the efficacy of these joint-preserving procedures. Newer resurfacing techniques have a role in treating articular surface loss. Hemiarthroplasty and total shoulder arthroplasty are recommended for patients with end-stage disease. PMID- 19474445 TI - Static and mobile antibiotic-impregnated cement spacers for the management of prosthetic joint infection. AB - Two-stage treatment is currently the most common approach for management of an infected joint prosthesis in the United States. Static antibiotic-impregnated polymethylmethacrylate cement spacers have traditionally been used; increasingly, however, mobile or articulating spacers are being utilized. Advocates of mobile spacers have cited potential advantages, including more effective maintenance of the joint space, allowing for limited weight bearing and facilitating joint motion; possible reduction in bone loss; and local delivery of antibiotics. Because a variety of materials and construction methods is used to make knee and hip spacers, comparisons are difficult. Randomized, prospective studies are needed to determine the best spacers for total knee and total hip arthroplasties. PMID- 19474446 TI - Complications of volar plate fixation for managing distal radius fractures. AB - Volar locking plate fixation via open reduction and internal fixation is an increasingly accepted method for managing displaced distal radius fractures. Volar plating offers biomechanically stable fixation, allows early rehabilitation, and enables fixation of comminuted or osteopenic bone. The literature reporting complications of volar plate fixation is limited primarily to case reports and small case series. The surgeon must be mindful of potential soft-tissue, neurovascular, and osseous complications, such as extensor tendon and flexor tendon injury, flexor pollicis rupture, carpal tunnel syndrome, complex regional pain syndrome, and loss of reduction, as well as hardware failure. Increased awareness of potential complications may lead to more prompt recognition and treatment when they do arise. PMID- 19474447 TI - Sagittal plane deformity in the adult patient. AB - Recent studies have demonstrated that sagittal balance is the most important and reliable radiographic predictor of clinical health status in the adult with a spinal deformity. Affected persons typically present with intractable pain, early fatigue, and a perception of being off-balance. Nonsurgical management with nonsteroidal and analgesic medications as well as physical therapy plays a limited role. Surgical correction is the primary method of alleviating symptoms. The surgical approach depends largely on the amount of correction required to restore overall balance. Options include posterior-only or combined anterior posterior surgery. The decision-making process often includes posterior-based osteotomies, such as the Smith-Petersen or pedicle subtraction, or vertebral column resection. Regardless of approach or osteotomy technique, spinal fusion with restored sagittal balance is the goal of any reconstructive procedure. PMID- 19474448 TI - Diagnosis of carpal tunnel syndrome. AB - This clinical practice guideline was created to improve patient care by outlining the appropriate information-gathering and decision-making processes involved in managing the diagnosis of carpal tunnel syndrome. The methods used to develop this clinical practice guideline were designed to combat bias, enhance transparency, and promote reproducibility. The guideline's recommendations are as follows: The physician should obtain an accurate patient history. The physician should perform a physical examination of the patient that may include personal characteristics as well as performing a sensory examination, manual muscle testing of the upper extremity, and provocative and/or discriminatory tests for alternative diagnoses. The physician may obtain electrodiagnostic tests to differentiate among diagnoses. This may be done in the presence of thenar atrophy and/or persistent numbness. The physician should obtain electrodiagnostic tests when clinical and/or provocative tests are positive and surgical management is being considered. If the physician orders electrodiagnostic tests, the testing protocol should follow the American Academy of Neurology/American Association of Neuromuscular and Electrodiagnostic Medicine/American Academy of Physical Medicine and Rehabilitation guidelines for diagnosis of carpal tunnel syndrome. In addition, the physician should not routinely evaluate patients suspected of having carpal tunnel syndrome with new technology, such as magnetic resonance imaging, computed tomography, and pressure-specified sensorimotor devices in the wrist and hand. This decision was based on an additional nonsystematic literature review following the face-to-face meeting of the work group. PMID- 19474449 TI - Treatment of carpal tunnel syndrome. AB - In September 2008, the Board of Directors of the American Academy of Orthopaedic Surgeons approved a clinical practice guideline on the treatment of carpal tunnel syndrome. This guideline was subsequently endorsed by the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. The guideline makes nine specific recommendations: A course of nonsurgical treatment is an option in patients diagnosed with carpal tunnel syndrome. Early surgery is an option with clinical evidence of median nerve denervation or when the patient so elects. Another nonsurgical treatment or surgery is suggested when the current treatment fails to resolve symptoms within 2 to 7 weeks. Sufficient evidence is not available to provide specific treatment recommendations for carpal tunnel syndrome associated with such conditions as diabetes mellitus and coexistent cervical radiculopathy. Local steroid injection or splinting is suggested before considering surgery. Oral steroids or ultrasound are options. Carpal tunnel release is recommended as treatment. Heat therapy is not among the options to be used. Surgical treatment of carpal tunnel syndrome by complete division of the flexor retinaculum is recommended. Routine use of skin nerve preservation and epineurotomy is not suggested when carpal tunnel release is performed. Prescribing preoperative antibiotics for carpal tunnel surgery is an option. It is suggested that the wrist not be immobilized postoperatively after routine carpal tunnel surgery. It is suggested that instruments such as the Boston Carpal Tunnel Questionnaire and the Disabilities of the Arm, Shoulder, and Hand questionnaire be used to assess patient responses to carpal tunnel syndrome treatment for research. PMID- 19474451 TI - How I treat von Willebrand disease. AB - Recent multicenter studies have clarified the molecular basis underlying the different von Willebrand disease (VWD) types, all of which are caused by the deficiency and/or abnormality of von Willebrand factor (VWF). These studies have suggested a unifying pathophysiologic concept. The diagnosis of VWD, remains difficult because its clinical and laboratory phenotype is very heterogeneous and may overlap with normal subjects. Stringent criteria are therefore required for a clinically useful diagnosis. In this paper, we delineate a practical approach to the diagnosis and treatment of VWD. Our approach is based on the critical importance of a standardized bleeding history that has been condensed into a final bleeding score and a few widely available laboratory tests, such as VWF ristocetin cofactor activity, VWF antigen and factor VIII. This approach would help identify those subjects who will probably benefit from a diagnosis of VWD. The next step involves performing a trial infusion with desmopressin in all patients who fail to exhibit an enhanced responsiveness to ristocetin. On the basis of these results and through a series of illustrative examples, the clinician will be able to select the best approach for the optimal management of VWD, according to the patient's characteristics and clinical circumstances. PMID- 19474450 TI - A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction. AB - We show that lentiviral delivery of human gamma-globin gene under beta-globin regulatory control elements in hematopoietic stem cells (HSCs) results in sufficient postnatal fetal hemoglobin (HbF) expression to correct sickle cell anemia (SCA) in the Berkeley "humanized" sickle mouse. Upon de-escalating the amount of transduced HSCs in transplant recipients, using reduced-intensity conditioning and varying gene transfer efficiency and vector copy number, we assessed critical parameters needed for correction. A systematic quantification of functional and hematologic red blood cell (RBC) indices, organ pathology, and life span was used to determine the minimal amount of HbF, F cells, HbF/F-cell, and gene-modified HSCs required for correcting the sickle phenotype. We show that long-term amelioration of disease occurred (1) when HbF exceeded 10%, F cells constituted two-thirds of the circulating RBCs, and HbF/F cell was one-third of the total hemoglobin in sickle RBCs; and (2) when approximately 20% gene-modified HSCs repopulated the marrow. Moreover, we show a novel model using reduced intensity conditioning to determine genetically corrected HSC threshold that corrects a hematopoietic disease. These studies provide a strong preclinical model for what it would take to genetically correct SCA and are a foundation for the use of this vector in a human clinical trial. PMID- 19474453 TI - Screening for hearing loss in the elderly using distortion product otoacoustic emissions, pure tones, and a self-assessment tool. AB - PURPOSE: To determine whether distortion product otoacoustic emissions (DPOAEs) could be used as a hearing screening tool with elderly individuals living independently, and to compare the utility of different screening protocols: (a) 3 pure-tone screening protocols consisting of 30 dB HL at 1, 2, and 3 kHz; 40 dB HL at 1, 2, and 3 kHz; or 40 dB HL at 1 and 2 kHz; (b) the Hearing Handicap Inventory for the Elderly-Screening version (HHIE-S); (c) pure tones at 40 dB HL at 1 and 2 kHz plus the HHIE-S; and (d) DPOAEs. METHOD: A total of 106 elderly individuals age 65-91 years were screened using the above protocols. RESULTS: Pass/fail results showed that most individuals failed at 30 dB HL, followed by DPOAEs, the 40-dB HL protocols, the HHIE-S alone, and the combined pure-tone/HHIE S protocol. All screening results were associated except the HHIE-S and 30 dB HL and the HHIE-S and DPOAEs. A McNemar analysis revealed that the differences between the correlated pass/fail results were significant except for the HHIE-S and 40 dB at 1 and 2 kHz. CONCLUSION: DPOAEs can be used to screen the elderly, with the advantage that individuals do not have to voluntarily respond to the test. PMID- 19474452 TI - Perioperative genomic profiles using structure-specific oligonucleotide probes. AB - OBJECTIVES: Many complications in the perioperative interval are associated with genetic susceptibilities that may be unknown in advance of surgery and anesthesia, including drug toxicity and inefficacy, thrombosis, prolonged neuromuscular blockade, organ failure and sepsis. The aims of this study were to design and validate the first genetic testing platform and panel designed for use in perioperative care, to establish allele frequencies in a target population, and to determine the number of mutant alleles per patient undergoing surgery. DESIGN/SETTING/PARTICIPANTS AND METHODS: One hundred fifty patients at Marshfield Clinic, Marshfield, Wisconsin, 100 patients at the Medical College of Wisconsin Zablocki Veteran's Administration Medical Center, Milwaukee, Wisconsin, and 200 patients at the University of Wisconsin Hospitals and Clinics, Madison, Wisconsin undergoing surgery and anesthesia were tested for 48 polymorphisms in 22 genes including ABC, BChE, ACE, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, beta2AR, TPMT, F2, F5, F7, MTHFR, TNFalpha, TNFbeta, CCR5, ApoE, HBB, MYH7, ABO and Gender (PRKY, PFKFB1). Using structure-specific cleavage of oligonucleotide probes (Invader, Third Wave Technologies, Inc., Madison, WI), 96-well plates were configured so that each well contained reagents for detection of both the wild type and mutant alleles at each locus. RESULTS: There were 21,600 genotypes confirmed in duplicate. After withdrawal of polymorphisms in non-pathogenic genes (i.e., the ABO blood group and gender-specific alleles), 376 of 450 patients were found to be homozygous for mutant alleles at one or more loci. Modes of two mutant homozygous loci and 10 mutant alleles in aggregate (i.e., the sum of homozygous and heterozygous mutant polymorphisms) were observed per patient. CONCLUSIONS: Significant genetic heterogeneity that may not be accounted for by taking a family medical history, or by obtaining routine laboratory test results, is present in most patients presenting for surgery and may be detected using a newly developed genotyping platform. PMID- 19474454 TI - Familial aggregation of age-related hearing loss in an epidemiological study of older adults. AB - PURPOSE: To estimate the genetic contributions to presbycusis. METHOD: Presbycusis was assessed by audiometric measurements at 3 waves of the population based Epidemiology of Hearing Loss Study (EHLS). Measurements from the most recent hearing examination were used, at which time the subjects (3,510 participants from the EHLS study) were between 48 and 100 years of age. Heritability of presbycusis was estimated using maximum likelihood methods in 973 biological relative pairs from 376 families. Familial aggregation was also evaluated by tetrachoric correlations, odds ratios, and lambda statistics in 594 sibling pairs from 373 sibships. RESULTS: The prevalence of presbycusis conformed to previous research, increasing with age and male sex. Heritability estimates for presbycusis adjusted for age, sex, education level, and exposure to work noise exceeded 50%, and siblings of an affected relative were at 30% higher risk. When stratified by sex, estimates of familial aggregation were higher in women than men. CONCLUSIONS: There is evidence that genetic factors contribute to age related hearing loss in this population-based sample. The familial aggregation is stronger in women than in men. PMID- 19474455 TI - Affecting others: social appraisal and emotion contagion in everyday decision making. AB - In a diary study of interpersonal affect transfer, 41 participants reported on decisions involving other people over 3 weeks. Reported anxiety and excitement were reliably related to the perceived anxiety and excitement of another person who was present during decision making. Risk and importance appraisals partially mediated effects of other's anxiety on own anxiety as predicted by social appraisal theory. However, other's emotion remained a significant independent predictor of own emotion after controlling for appraisals, supporting the additional impact of more direct forms of affect transfer such as emotion contagion. Significant affect-transfer effects remained even after controlling for participants' perceptions of the other's emotion in addition to all measured appraisals, confirming that affect transfer does not require explicit registration of someone else's feelings. This research provides some of the clearest evidence for the operation of both social appraisal and automatic affect transfer in everyday social life. PMID- 19474456 TI - Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity. AB - Hepatocytes expressing liver fatty acid binding protein (L-FABP) are known to be more resistant to oxidative stress than those devoid of this protein. The mechanism for the observed antioxidant activity is not known. We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrupole time-of-flight MS after being digested by endoproteinase Glu-C. L-FABP was observed to have better antioxidative activity when free radicals were generated by the hydrophilic generator than by the lipophilic generator. Oxidative modification of L-FABP included up to five methionine oxidative peptide products with a total of approximately 80 Da mass shift compared with native L-FABP. Protection against lipid peroxidation of L-FABP after binding with palmitate or alpha-bromo palmitate by the AAPH or AMVN free radical generators indicated that ligand binding can partially block antioxidant activity. We conclude that the mechanism of L-FABP's antioxidant activity is through inactivation of the free radicals by L-FABP's methionine and cysteine amino acids. Moreover, exposure of the L-FABP binding site further promotes its antioxidant activity. In this manner, L-FABP serves as a hepatocellular antioxidant. PMID- 19474457 TI - The antifungal drug voriconazole is an efficient inhibitor of brain cholesterol 24S-hydroxylase in vitro and in vivo. AB - Cholesterol 24S-hydroxylase (CYP46A1) is of key importance for cholesterol homeostasis in the brain. This enzyme seems to be resistant toward most regulatory factors and at present no drug effects on its activity have been described. The crystal structures of the substrate-free and substrate-bound CYP46A1 were recently determined (Mast et al., Crystal structures of substrate bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc. Natl. Acad. Sci. USA. 2008. 105: 9546-9551). These structural studies suggested that ligands other than sterols can bind to CYP46A1. We show here that the antifungal drug voriconazole binds to the enzyme in vitro and inhibits CYP46A1-mediated cholesterol 24-hydroxylation with a Ki of 11 nM. Mice treated with daily intraperitoneal injections of voriconazole for 5 days had high levels of voriconazole in the brain and significantly reduced brain levels of 24S-hydroxycholesterol. The levels of squalene, lathosterol, and HMG CoA reductase mRNA were reduced in the brain of the voriconazole-treated animals as well, indicating a reduced cholesterol synthesis. Most of this effect may be due to a reduced utilization of cholesterol by CYP46A1. One of the side-effects of voriconazole is visual disturbances. Because CYP46A1 is also expressed in the neural retina, we discuss the possibility that the inhibition of CYP46A1 by voriconazole contributes to these visual disturbances. PMID- 19474458 TI - Metabolic precursors of surfactant disaturated-phosphatidylcholine in preterms with respiratory distress. AB - Our objective was to study the metabolic precursors of surfactant disaturated phosphatidylcholine (DSPC) in preterm infants with respiratory distress syndrome (RDS) on mechanical ventilation. We performed 46 DSPC kinetic studies in 23 preterms on fat-free parenteral nutrition and mechanical ventilation (birth weight = 1167 +/- 451 g, gestational age = 28.5 +/- 2.0 weeks). Eight infants received a simultaneous intravenous infusion of U(13)C-glucose and [16,16,16](2)H palmitate, eight infants received U(13)C-glucose and (2)H(2)O, and seven received U(13)C-palmitate and (2)H(2)O. Surfactant DSPC kinetics were calculated from the isotopic enrichments of DSPC-palmitate from sequential tracheal aspirates and its metabolic precursors in plasma or urine. DSPC fractional synthesis rate (FSR) was 17 +/- 11, 21 +/- 16, and 15 +/- 6%/day from glucose, palmitate, and body water, respectively (P = 0.36). DSPC-FSR from U(13)C-glucose and (2)H(2)O were significantly correlated and yielded similar estimates (difference of -0.1 +/- 3%) (P = 0.91). The difference in the 15 infants receiving palmitate versus (2)H(2)O or palmitate versus glucose was +6.0 +/- 12%/day (P = 0.21). There was a significant correlation between DSPC-FSRs from plasma glucose and plasma FFA. The contribution of glucose versus palmitate to DSPC-FSR was 49 +/- 20% versus 51 +/- 20%, respectively. Plasma glucose and FFA showed similar contributions to DSPC FSR in infants with RDS and fat-free parenteral nutrition. FSRs from (2)H(2)O or glucose were highly correlated. PMID- 19474459 TI - World collaborative report on Assisted Reproductive Technology, 2002. AB - The International Committee for Monitoring Assisted Reproductive Technology's (ICMART) Eighth World Report analyzes assisted reproductive technology (ART) practice and results for the year 2002 from 53 countries by type of ART, women's age, number of embryos transferred and multiple births. Over 601,243 initiated cycles resulted in a delivery rate (DR) per aspiration of 22.4% for conventional IVF, 21.2% for ICSI and a DR per transfer of 15.3% for frozen embryo transfer. For conventional IVF and ICSI, there was an overall twin rate of 25.7% per delivery and a triplet rate of 2.5%. The number of babies born worldwide through ART in 2002 was estimated to range between 219,000 and 246,000. There were wide variations in availability, DRs and multiple birth rates across the countries. Compared with the previous report (year 2000), there was a large increase in the number of cycles and a slight increase in the DR. There was a marginal decline in the mean number of embryos transferred and in the multiple DRs. PMID- 19474460 TI - Increase in teachers' knowledge about ADHD after a week-long training program: a pilot study. AB - OBJECTIVES: ADHD affects 3% to 5% of school-age children. Clinical and community based epidemiological studies in Pakistan have shown a high prevalence of ADHD among school going children. A thorough review of literature shows that no studies of teachers' training programs regarding ADHD have been published in Pakistani research literature. The aim of the present study is the development and evaluation of an ADHD training program for teachers. METHODS: A teachers' training program for ADHD was designed and a pilot run in 3 schools of Karachi, Pakistan. Teachers knowledge regarding signs and symptoms of ADHD was tested before and after the workshop and then again after 6 months using an ADHD knowledge questionnaire. RESULTS: Forty-nine teachers, all of them women, completed the questionnaires before and after the training program, and 35 of them filled it out at the 6-month interval. Mean scores of these tests were compared using a paired t test. The authors found the difference of mean score of 1.48 +/- 2.95, and this was statistically significant (p < .005). CONCLUSION: The authors conclude that the workshop improved the knowledge of the school teachers regarding ADHD symptomatology, and it remained significant even after 6 months of training. PMID- 19474461 TI - Atomoxetine versus stimulants in the community treatment of children with ADHD: an electronic diary study. AB - OBJECTIVE: To compare the morning and afternoon/evening functioning of children with ADHD treated in the community with either atomoxetine or long-acting stimulants and reported to be doing well. METHOD: 109 8- to 12-year-olds and their mothers participated in one of three groups: stimulants (STIM, N = 26), atomoxetine (ATMX, N = 25), or comparison (COMP, N = 58). Mothers completed morning and evening electronic diaries installed on personal digital assistants throughout an entire week, rating the child's behaviors and moods as well as their own moods and perceptions. RESULTS: There was no evidence that ongoing pharmacotherapy fully normalized the behaviors of children with ADHD: Mothers in both ADHD groups reported higher rates of child inattention, hyperactivity/impulsivity, oppositionality, and negative affect and lower levels of parenting efficacy and positive affect than did COMP mothers. Although the behavioral profiles were generally comparable for the STIM and ATMX groups, there were indications of better functioning in the ATMX group during mornings only. CONCLUSION: Children treated in the community with either STIM or ATMX appear to have similar behavioral profiles, suggesting that medication decisions be guided by other factors such as comorbid disorders, child and parent preferences, and effects on nontargeted behaviors and moods. PMID- 19474462 TI - Work performance differences between college students with and without ADHD. AB - OBJECTIVE: This study examines the difference between college students with and without Attention Deficit/ Hyperactivity Disorder (ADHD) in regard to their work performance. METHOD: A series of ANOVAs analyzed group differences in symptoms experienced at work. The independent variable was group (i.e., ADHD, Controls). The dependent variables include items from Barkley's "Work Performance Rating Scale" (Barkley & Murphy, 1998), which assesses the degree to which symptoms of inattention, hyperactivity and impulsivity are evident on the job. For the group with ADHD, the relationship between symptom severity and indicators of work performance (e.g., number of times fired, overall rating of work performance) was also examined, using correlational analyses. Descriptive analyses were also used to examine which items were most frequently endorsed by the group with ADHD, as well as which areas of work were most affected by ADHD symptoms. RESULTS: Results reveal that ADHD has a detrimental impact on the work performance of college students in multiple areas. Severity of symptoms was unrelated to number of times fired from a job and the overall indicator of work performance. CONCLUSION: College students with ADHD do exhibit more on-the-job difficulties than their non ADHD peers, and thus may require extra support with their work-related endeavors. PMID- 19474463 TI - Self-reported ADHD and adjustment in college: cross-sectional and longitudinal findings. AB - OBJECTIVE: To examine the association between self-reported ADHD and college adjustment. PARTICIPANTS: Study 1 included nearly 3400 undergraduates attending a public and private university. Study 2 included 846 students who participated during freshman and sophomore year. METHOD: Students completed a web-based survey that assessed diagnostic status and adjustment in multiple domains. RESULTS: Relative to other students, those with self-reported ADHD had lower GPAs and reported more academic concerns, depressive symptoms, social concerns, emotional instability, and substance use. Overall, however, most were making satisfactory adjustments in these domains. Benefits of medication treatment were not found. Freshman year ADHD predicted lower GPA, increased academic concerns and alcohol use, and smoking initiation. CONCLUSION: Students with ADHD struggled relative to peers but most were adjusting reasonably well across multiple domains. Future research should move beyond the use of self-reported diagnosis and more carefully examine the impact of medication treatment in this population. PMID- 19474464 TI - Virological relapse in chronic hepatitis C. AB - Approximately one-third of all patients infected with hepatitis C virus (HCV) genotype 1 who complete pegylated interferon alpha based therapy and have undetectable serum HCV RNA at the end of treatment will experience relapse. Although relapse is a common outcome of therapy, its pathology and strategies for optimal management are poorly understood; however, optimized ribavirin dosing is recognized as pivotal in mitigating relapse. Recent data also suggest that early viral kinetics might help identify particular patient groups, such as slow responders, who are predisposed to relapse. This review provides a comprehensive overview of the importance of relapse in patients with chronic hepatitis C, including its underlying pathobiology, potential predictors and strategies to optimize the retreatment of previous relapsers. PMID- 19474465 TI - Plasma efavirenz concentrations and the association with CYP2B6-516G >T polymorphism in HIV-infected Thai children. AB - BACKGROUND: Concerns have been raised about the possibility of subtherapeutic efavirenz (EFV) plasma levels in children with the current dosing guideline. Single nucleotide polymorphisms of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene have been associated with high interindividual variations in EFV plasma concentrations. Our objective was to determine the adequacy of EFV dosing and explore the influence of CYP2B6-516G>T polymorphisms on EFV plasma concentrations in Thai HIV-infected children. METHODS: A total of 63 HIV-infected children receiving EFV for > or =4 weeks were assessed. Children received EFV daily doses on the basis of body weight bands. Between 12 to 16 h after EFV intake, a blood sample was drawn to measure the EFV plasma concentration and to determine the CYP2B6-516G>T polymorphism using HPLC and direct gene sequencing, respectively. RESULTS: The median age (range) was 12.3 years (3.1-18.7). The mean (+/-sd) EFV plasma concentration was 3,138 ng/ml (3,313). Eight (13%), 45 (71%) and 10 (16%) children had an EFV concentration <1,000 ng/ml, 1,000-4,000 ng/ml and >4,000 ng/ml, respectively. CYP2B6-516 G/G, G/T and T/T genotypes were found in 48%, 41% and 11% children, respectively. The CYP2B6-516G>T allele frequency was 31.75%. The mean (+/-sd) EFV concentration for children with G/G, G/T and T/T genotypes were 1,604 ng/ml (729), 2,635 ng/ml (1,199) and 11,582 ng/ml (2,972), respectively (P<0.001). A correlation between EFV concentrations >4,000 ng/ml and psychiatric side effects was observed (P=0.02), but there was no association with rash, hepatotoxicity or central nervous system disturbances. CONCLUSIONS: Current EFV dosing guidelines provide adequate plasma drug concentrations in Thai HIV infected children. CYP2B6-516G>T polymorphisms significantly affect the drug metabolism of EFV in children. PMID- 19474466 TI - Early initiation of highly active antiretroviral therapy fails to reverse immunovirological abnormalities in gut-associated lymphoid tissue induced by acute HIV infection. AB - BACKGROUND: During the acute phase of HIV infection, large CD4+ T-cell depletion occurs in the gastrointestinal tract. The kinetics of CD4+ T-cell decrease and highly active antiretroviral therapy (HAART)-mediated immune reconstitution were evaluated. METHODS: Rectosigmoid colonic (RSC) biopsies and blood samples of nine patients with acute HIV infection were collected. CD4+ T-cell count, HIV RNA, intracellular HIV DNA and messenger RNA cytokine expression were evaluated before and after 6 months of HAART. RESULTS: All nine patients presented symptomatic retroviral infection. Early HAART was associated with a sustained and comparable reduction of HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs) and RSC biopsies. HIV DNA decreased in PBMCs, but was only marginally reduced in RSC biopsies. Comparisons between reduction rates of HIV DNA in these two compartments confirmed that HIV DNA clearance was less efficient in RSC biopsies compared with PBMCs. Assessment of immunological profiles in PBMCs and RSC biopsies showed that the T-helper (Th)1-like/Th2-like ratio was sharply decreased in RSC biopsies and increased in PBMCs throughout the study period. A persistent Th2-like profile was detected in RSC biopsies. Efficient clearing of HIV DNA observed in PBMCs correlated with the establishment of a more favourable Th1-like profile. CONCLUSIONS: A less efficient clearance of intracellular HIV DNA following early introduction of HAART is associated with persistent immunological impairment in gut-associated lymphoid tissue (GALT), which is reflected by the skewed expression of cytokines in this reservoir. The present study shows that early initiation of HAART, in the short-term, is not effective in containing the establishment of HIV infection and in reversing associated immunological GALT abnormalities. PMID- 19474467 TI - Mitochondrial toxicity in HIV type-1-exposed pregnancies in the era of highly active antiretroviral therapy. AB - BACKGROUND: The aim of this study was to determine the effects of HIV type-1 (HIV 1) infection and antiretroviral therapy (ART) on placental mitochondria. METHODS: HIV-1-infected pregnant women and HIV-1-uninfected controls were enrolled prospectively. Placental mitochondrial DNA (mtDNA) copy numbers were determined by quantitative PCR, subunits II and IV of cytochrome c oxidase (COX) were quantified by western blot and mitochondrial ultrastructure was evaluated by electron microscopy. Venous blood lactate was measured in newborns. RESULTS: In total, 45 HIV-1-infected pregnant women on ART and 32 controls were included. Mean +/-sd mtDNA copy numbers were significantly reduced in ART and HIV-1-exposed placentas (240 +/-118 copies/cell) in comparison with controls (686 +/-842 copies/cell; P<0.001). The mean COX II/IV ratio was 48% lower in the investigational group compared with controls (P<0.001). There was no evidence of severe ultrastructural damage within mitochondria of HIV-1-infected ART-exposed placentas. Although lactate levels between newborns did not differ, they were negatively correlated with placental mtDNA levels. There was no clear association between mitochondrial parameters and a particular nucleoside reverse transcriptase inhibitor (NRTI), the number of NRTIs or time of NRTI exposure. CONCLUSIONS: Placental tissue of HIV-1-infected ART-exposed pregnancies shows evidence of mtDNA depletion with secondary respiratory chain compromise. The clinical effects of this finding warrant further investigation. PMID- 19474468 TI - Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-infected patients. AB - BACKGROUND: The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring. METHODS: Cross-sectional VL sampling of HIV-1 infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped. RESULTS: Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53 15.70). CONCLUSIONS: Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings. PMID- 19474469 TI - Self-reported alcohol consumption and its association with adherence and outcome of antiretroviral therapy in the Swiss HIV Cohort Study. AB - BACKGROUND: Alcohol consumption leading to morbidity and mortality affects HIV infected individuals. Here, we aimed to study self-reported alcohol consumption and to determine its association with adherence to antiretroviral therapy (ART) and HIV surrogate markers. METHODS: Cross-sectional data on daily alcohol consumption from August 2005 to August 2007 were analysed and categorized according to the World Health Organization definition (light, moderate or severe health risk). Multivariate logistic regression models and Pearson's chi(2) statistics were used to test the influence of alcohol use on endpoints. RESULTS: Of 6,323 individuals, 52.3% consumed alcohol less than once a week in the past 6 months. Alcohol intake was deemed light in 39.9%, moderate in 5.0% and severe in 2.8%. Higher alcohol consumption was significantly associated with older age, less education, injection drug use, being in a drug maintenance programme, psychiatric treatment, hepatitis C virus coinfection and with a longer time since diagnosis of HIV. Lower alcohol consumption was found in males, non-Caucasians, individuals currently on ART and those with more ART experience. In patients on ART (n=4,519), missed doses and alcohol consumption were positively correlated (P<0.001). Severe alcohol consumers, who were pretreated with ART, were more often off treatment despite having CD4+ T-cell count <200 cells/microl; however, severe alcohol consumption per se did not delay starting ART. In treated individuals, alcohol consumption was not associated with worse HIV surrogate markers. CONCLUSIONS: Higher alcohol consumption in HIV-infected individuals was associated with several psychosocial and demographic factors, non-adherence to ART and, in pretreated individuals, being off treatment despite low CD4+ T-cell counts. PMID- 19474470 TI - Evolution and predictors of HIV type-1 drug resistance in patients failing combination antiretroviral therapy in Italy. AB - BACKGROUND: This study aimed to examine the evolution of genotypic drug resistance prevalence in treatment-failing patients in the multicentre, Italian, Antiretroviral Resistance Cohort Analysis (ARCA). METHODS: Patients with a drug resistance genotype test performed between 1999 and 2006 at failure of a combination antiretroviral therapy and with complete treatment history were selected. The prevalence of resistance was measured overall, per calendar year, per drug class and per treatment line at failure. RESULTS: The overall resistance prevalence was 81%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs) declined after 2002 (68% in 2006; chi(2) for trend P=0.004); resistance to non-NRTIs (NNRTIs) stabilized after 2004; and resistance to protease inhibitors (PIs) declined after 2001 (43% in 2006; P=0.004). In first-line failures, NRTI resistance decreased after 2002 (P=0.006), NNRTI resistance decreased after 2003 (P=0.001) and PI resistance decreased after 2001 (P<0.001). Independent predictors of resistance to any class were HIV type-1 transmission by heterosexual contacts as compared with injecting drug use, a higher number of experienced regimens, prior history of suboptimal therapy, higher viral load and CD4+ T-cell counts, more recent calendar year and viral subtype B carriage, whereas the use of PI-based versus NNRTI-based regimens at failure was associated with a reduced risk of resistance. There was an increase of type-1 thymidine analogue and of protease mutations L33F, I47A/V, I50V and I54L/M, whereas L90M decreased over calendar years. CONCLUSIONS: During more recent years, emerging drug resistance has decreased, particularly in first-line failures. The prevalence continues to be high in multiregimen-failing patients. PMID- 19474471 TI - Incidence of lipodystrophy and metabolic disorders in patients starting non nucleoside reverse transcriptase inhibitors in Benin. AB - BACKGROUND: The incidence and risk factors for lipodystrophy and metabolic disorders among patients in Africa on first-line combined antiretroviral treatment (cART) mostly containing non-nucleoside reverse transcriptase inhibitors is poorly documented. METHODS: This prospective cohort study recruited 88 HIV-infected patients initiating cART between October 2004 and June 2005 in Cotonou, Benin. Patients were followed for 24 months. The main outcomes were incidence of lipodystrophy and metabolic disorders. Multivariate Cox proportional hazards regression models were used to describe factors associated with progression to lipodystrophy. RESULTS: After a median follow-up of 23.2 months (interquartile range 22.3-23.7), 24 (30%) patients developed lipodystrophy (lipoatrophy 9%, lipohypertrophy 24% and mixed pattern 2.5%). The incidence rate for lipodystrophy was estimated to 1.72 per person-month (95% confidence interval [CI] 1.15-2.56) occurring after a median time of 11 months on cART. Metabolic syndrome (International Diabetes Federation definition) appeared in 10 (13%) patients after a median of 15 months with an estimated incidence rate of 0.62 per person-month (95% CI 0.33-1.16). It was more common in women (19.2% versus 3.1% in men; P=0.043). Diabetes (8%) and hypercholesterolaemia (35%) were also observed. After adjustment, gender, young age (hazard ratio [HR] 0.45 [95% CI 0.22-0.90]; P=0.025), high BMI at inclusion (HR 1.53 [95% CI 1.28-1.83]; P<0.0001) and smoking (HR 28.0 [95% CI 2.5-307.4]; P=0.006) were significantly associated with lipohypertrophy. CONCLUSIONS: Lipodystrophy and metabolic syndrome were commonly and rapidly observed in this cohort of sub-Saharan patients initiating cART. PMID- 19474472 TI - Predictive value of immune parameters before treatment interruption (TI) for CD4+ T-cell count change during TI in HIV infection. AB - BACKGROUND: Despite the contraindications, stopping treatment for HIV infection continues to be a common practice. Understanding whether T-cell proliferative capacity and phenotypic markers before treatment interruption (TI) can predict CD4+ T-cell count change and nadir during TI would be clinically useful. METHODS: This retrospective study included 27 HIV-infected patients in the chronic phase of infection while on combination antiretroviral therapy (cART) who underwent a TI. Peripheral blood mononuclear cells from a baseline pre-TI time point were screened for T-cell proliferation to cytomegalovirus (CMV) lysate, an HIV Gag p55 peptide pool as well as positive and negative control stimuli. CD28 and CD57 expression on CD4+ and CD8+ T-cells were measured. RESULTS: Baseline viral load, CD4+ T-cell count, pre-cART nadir CD4+ T-cell and percentage CD4+CD28+ T-cells were all predictive of the lowest CD4+ T-cell count during TI (Spearman's correlation P<0.05 for all analyses). In addition, CD4+ and CD8+ T-cells proliferation to CMV lysate, baseline CD4+ T-cell count and percentage CD4+CD57+ T-cells correlated negatively with CD4+ T-cell decrease during TI (Spearman's correlation P<0.05 for all analyses). CONCLUSIONS: In treated chronic HIV infected patients, pre-TI immune parameters are potential predictors for both the nadir CD4+ T-cell count and CD4+ T-cell count decrease during TI. PMID- 19474473 TI - Long-term hepatitis C internal ribosome entry site-dependent gene expression mediated by phage phiC31 integrase in mouse model. AB - BACKGROUND: The lack of a robust small animal model for hepatitis C virus (HCV) has hindered the development of novel drugs, including internal ribosome entry site (IRES) inhibitors. Phage phiC31 integrase has emerged as a potent tool for achieving long-term gene expression in vivo. This study utilized phiC31 integrase to develop a stable, reproducible and easily accessible HCV IRES mouse model. METHODS: phiC31 integrase plasmid and the reporter vector, HCV-IRES-luciferase expression cassette (containing an attB site), was codelivered to murine livers using high pressure tail vein injection. HCV IRES-dependent translation reflected by luciferase expression was accurately monitored in vivo by bioluminescence imaging. Genomic integration of the transgene was confirmed by partial hepatectomy and nested PCR. An HCV IRES-targeted short hairpin RNA (shRNA) expression plasmid, sh184, was hydrodynamically transfected into mouse liver to study its inhibition efficacy in vivo. RESULTS: phiC31 integrase mediated intramolecular recombination between wild-type attB and attP sites in mice. The expression of luciferase was stable after 30 days post-transfection and remained so for 300 days only in the livers of mice that were coinjected with the integrase-encoding plasmid. Luciferase levels reduced dramatically after hydrodynamic transfection of sh184. CONCLUSIONS: These results indicate that this mouse model provides a powerful tool for accurate and long-term evaluation of potential anti-IRES compounds in vivo. PMID- 19474474 TI - Evaluation of transmitted HIV drug resistance among recently-infected antenatal clinic attendees in four Central African countries. AB - BACKGROUND: The rapid expansion of antiretroviral treatment in resource-limited settings is raising concerns regarding the emergence and transmission of HIV drug resistance (HIVDR). We evaluated the extent of transmission of drug-resistant HIV strains in four Central African countries: the Republic of Congo, Central African Republic, Chad and Cameroon. METHODS: The World Health Organization (WHO) HIVDR threshold survey was implemented in major treatment areas in each country. Pregnant women who were aged <25 years, who were at first pregnancy and who were HIV type-1-positive were enrolled at each site in 2006-2007 for genotyping. HIVDR prevalence was categorized using the WHO threshold survey binomial sequential sampling method. RESULTS: The prevalence of HIVDR in Brazzaville and Bangui sites could not be classified because the eligible sample number was not reached. HIVDR prevalence was low (<5%) in N'Djamena for all drug classes. In Yaounde, we found one individual with the D67D/N mutation and two with K103N. HIVDR prevalence was categorized as low (<5%) for protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), and moderate (> or =5-< or =15%) for non-NRTIs (NNRTIs). HIVDR prevalence in Douala was low for PIs and NNRTIs, and moderate for NRTIs as we identified one individual with M184V plus K101E plus G190A mutations and a second with D67D/N. CONCLUSIONS: The moderate HIVDR prevalence found in Yaounde and Douala indicate that efforts should be made in Cameroon to prevent HIVDR; however, additional surveys are needed to confirm this trend. This study highlighted challenges presented by the WHO methodology, such as additional costs, workload, difficulties in acquiring even small sample numbers and the necessity for better quality assurance of HIV testing and record keeping at antenatal clinics. PMID- 19474475 TI - Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env. AB - BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure. METHODS: Individuals with MDR HIV-1 receiving therapy for > or =3 months were included. CD4+ T-cell count slopes and pol and clonal env sequences were determined. Genetic analyses were performed using distance-based and maximum likelihood methods. Synonymous mutations rates of env were used to estimate viral replication. RESULTS: Of 1,000 patients treated between 1995 and 2003, 72 individuals fulfilled the definition for triple-class failure, but 25 were non compliant, 21 were successfully resuppressed and 3 had died or quit therapy. Of the 23 that fulfilled study criteria, 16 had samples available for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0.02). CONCLUSIONS: Our results suggest that minor PI mutations and NRTI mutations present early during therapy failure are predictive of the CD4+ T-cell count slopes. Synonymous mutation rates of the env gene suggested that underlying differences in fitness could cause this association. PMID- 19474476 TI - Pregnancy outcomes in women with HIV type-1 receiving a lopinavir/ritonavir containing regimen. AB - BACKGROUND: The pregnancy-related adverse effects of antiretroviral therapy (ART) have yielded discordant results, which could be explained in part by the heterogeneity of ART protocols. The objective of our study was to explore whether lopinavir/ritonavir (LPV/r) exposure during pregnancy is associated with adverse outcomes. METHODS: Data on 100 consecutive HIV type-1 (HIV-1)-infected women receiving LPV/r during pregnancy and who delivered after 15 weeks gestational age (GA) between January 2003 and June 2007 in a single centre were analysed. For each HIV-1-infected woman, two uninfected women matched by age, parity and geographical origin were selected among patients delivering during the same period. Preterm delivery (PTD), vasculoplacental complications, gestational glucose intolerance and post-partum complication rates were compared between cases and controls. Factors associated with PTD and post-partum complications were assessed in HIV-1-infected women by a logistic regression model. RESULTS: Rates of vasculoplacental complication and gestational glucose intolerance were not higher among HIV-1-infected women than in controls. PTD was higher in HIV-1 infected women (21%) than in controls (10%; P<0.01). In HIV-1-infected women, PTD was associated with HIV-1 RNA level > or =50 copies/ml at delivery (adjusted odds ratio 6.15, 95% confidence interval 1.83-20.63; P=0.003). No association was found between occurrence of PTD and LPV/r exposure before 14 weeks GA. CONCLUSIONS: In this population of HIV-1-infected pregnant women receiving LPV/r, the risk of PTD was higher than in HIV-1-uninfected controls. As PTD risk was not associated with early exposure to LPV/r, these data support current guidelines to initiate ART earlier in pregnancy. PMID- 19474477 TI - Investigation of expert rule bases, logistic regression, and non-linear machine learning techniques for predicting response to antiretroviral treatment. AB - BACKGROUND: The extreme flexibility of the HIV type-1 (HIV-1) genome makes it challenging to build the ideal antiretroviral treatment regimen. Interpretation of HIV-1 genotypic drug resistance is evolving from rule-based systems guided by expert opinion to data-driven engines developed through machine learning methods. METHODS: The aim of the study was to investigate linear and non-linear statistical learning models for classifying short-term virological outcome of antiretroviral treatment. To optimize the model, different feature selection methods were considered. Robust extra-sample error estimation and different loss functions were used to assess model performance. The results were compared with widely used rule-based genotypic interpretation systems (Stanford HIVdb, Rega and ANRS). RESULTS: A set of 3,143 treatment change episodes were extracted from the EuResist database. The dataset included patient demographics, treatment history and viral genotypes. A logistic regression model using high order interaction variables performed better than rule-based genotypic interpretation systems (accuracy 75.63% versus 71.74-73.89%, area under the receiver operating characteristic curve [AUC] 0.76 versus 0.68-0.70) and was equivalent to a random forest model (accuracy 76.16%, AUC 0.77). However, when rule-based genotypic interpretation systems were coupled with additional patient attributes, and the combination was provided as input to the logistic regression model, the performance increased significantly, becoming comparable to the fully data-driven methods. CONCLUSIONS: Patient-derived supplementary features significantly improved the accuracy of the prediction of response to treatment, both with rule based and data-driven interpretation systems. Fully data-driven models derived from large-scale data sources show promise as antiretroviral treatment decision support tools. PMID- 19474478 TI - The pharmacokinetics, safety and efficacy of boosted saquinavir tablets in HIV type-1-infected pregnant women. AB - BACKGROUND: Pregnancy affects the pharmacokinetics of most protease inhibitors. Saquinavir, when administered in a tablet formulation, has not been studied extensively in this setting. METHODS: A pharmacokinetic, prospective, multicentre trial of HIV type-1-infected pregnant women treated with saquinavir (500 mg tablets) boosted with ritonavir at a dose of 1,000/100 mg twice daily plus a nucleoside backbone was conducted. Pharmacokinetic curves were recorded for 12 h in the second trimester (week 20 +/-2), the third trimester (week 33 +/-2) and post-partum (weeks 4-6). Blood was sampled pre-dosing and at 1, 2, 3, 4, 6, 8, 10 and 12 h post-dosing. Pharmacokinetic parameters were calculated using WinNonlin software version 4.1. RESULTS: A total of 37 women were included in the analysis. Mean (+/-sd) values for saquinavir area under the curve (AUC(0-12h)) were 23.47 h*mg/l (11.92) at week 20 (n=16), 23.65 h*mg/l (9.07) at week 33 (n=31) and 25.00 h*mg/l (11.81) post-partum (n=9). There was no significant difference in the saquinavir AUC(0-12h) when comparing the data during pregnancy and post-partum. Subtherapeutic plasma concentrations of saquinavir (defined as <0.10 mg/l) were not observed throughout the study. No major safety concerns were noted. CONCLUSIONS: Saquinavir exposure in the new tablet formulation generates adequate saquinavir concentrations throughout the course of pregnancy and is safe to use; therefore, no dose adjustment during pregnancy is needed. PMID- 19474479 TI - CD4+ T-cell percentage is an independent predictor of clinical progression in AIDS-free antiretroviral-naive patients with CD4+ T-cell counts >200 cells/mm3. AB - BACKGROUND: The aim of this study was to evaluate the clinical prognostic value of the CD4+ T-cell percentage (%CD4), the CD4+/CD8+ T-cell ratio or the CD8+ T cell count, in addition to the CD4+ T-cell count and viral load (VL) in antiretroviral-naive HIV-infected patients with CD4+ T-cell counts >200 cells/mm(3). METHODS: Antiretroviral-naive patients (n=9,740) who were AIDS-free and had a CD4+ T-cell count >200 cells/mm(3) at their first visit after January 1997 were followed-up until treatment initiation or clinical progression (mean follow-up 17 months and 13,660 person-years). Poisson regression was used for statistical analyses. RESULTS: Progression to AIDS-defining events (ADEs), serious ADEs and death occurred in 228 patients (crude rate 1.69 per 100 person years), 105 patients (0.77 per 100 person-years) and 67 patients (0.49 per 100 person-years), respectively. Regarding progression to ADE, the data fit was improved when the model also included the %CD4 (Akaike's information criteria [AIC] 2,049) and, to a lesser extent, the CD4+/CD8+ T-cell ratio (AIC 2,053), in addition to CD4+ T-cell count and VL (AIC 2,056). After adjustment for VL and baseline characteristics, patients with CD4+ T-cell counts of 350-500 cells/mm(3) and %CD4<15% had an estimated incidence of ADE of 3 per 100 person-years, similar to that in patients with CD4+ T-cell counts of 200-350 cells/mm(3) and %CD4>15%. The %CD4 was also significantly associated with the risk of serious ADE. By contrast, %CD4, CD4+/CD8+ T-cell ratio or CD8+ T-cell count had no additional prognostic value for the risk of death. CONCLUSIONS: In antiretroviral-naive HIV infected patients with CD4+ T-cell counts >200 cells/mm(3), the %CD4 was predictive of the risk of clinical progression independently of CD4+ T-cell count and VL. PMID- 19474480 TI - Modelling hepatitis C virus kinetics: the relationship between the infected cell loss rate and the final slope of viral decay. AB - BACKGROUND: Patients infected with hepatitis C virus (HCV) who respond to treatment with interferon-alpha plus ribavirin exhibit biphasic or triphasic viral load decreases. While the rapid first phase is indicative of the effectiveness of therapy in blocking viral production (epsilon), the slope of the final phase (lambda), that is, the second phase in biphasic decreases and the third phase in triphasic decreases, depends on the infected cell loss rate (delta). In standard models, lambda is approximately epsilondelta when the viral clearance rate c>>delta, as has been previously estimated. METHODS: The relationship among epsilon, delta, lambda and the baseline fraction of HCV infected hepatocytes (pi) was investigated in a model that included proliferation of hepatocytes. RESULTS: We found that lambda was not proportional to epsilon, but rather obeyed a complex relationship that could lead to dramatic increases in estimates of delta as epsilon increased. In particular, when epsilon<99%, lambda moderately underestimated delta in patients with a small pi, whereas delta might be up to 10-fold larger than lambda in patients with a large pi. Interestingly, when epsilon>99%, delta approximately lambda regardless of pi. CONCLUSIONS: Our results indicated that in patients undergoing therapy who achieved a 2 log(10) reduction in viral load (epsilon<99%), previously estimated delta values might represent only a minimal estimate of the infected cell loss rate. Moreover, combining interferon-alpha with new antiviral agents to achieve epsilon>99% should allow for a more accurate estimate of delta in HCV RNA kinetic studies. This might be important when using viral kinetics to estimate the effect of the immune response on viral elimination and the attainment of sustained virological response. PMID- 19474481 TI - Recovering nutrients from wastewater treatment plants through struvite crystallization: CFD modelling of the hydrodynamics of UBC MAP fluidized-bed crystallizer. AB - This paper is an attempt to model the hydrodynamics of the UBC (University of British Columbia) MAP (magnesium ammonium phosphate) fluidized bed crystallizer. In this study, a numerical investigation of hydrodynamics of the UBC MAP crystallizer was performed, using commercial computational fluid dynamics (CFD) software, Fluent 6.3. One of the main findings of this modelling effort is the relative distribution of the different phases, in this case solids (struvite crystals) and liquid (water), within the reactor. This information is very important, in the sense that it helps fixing the size of the crystallizer, which can be a significant factor, affecting the total cost of the process. Another finding of this simulation is the volume fraction distribution of the different sizes of solid particles, which actually provides insight into the hydrodynamics of the reactor and will fill up the knowledge gap in developing an overall mechanistic model for the crystallizer. PMID- 19474482 TI - A novel sludge minimized biological nitrogen removal process for saline sewage treatment. AB - This study reports a lab-scale evaluation of a new biological nitrogen removal process for saline sewage treatment, namely a SANI process (Sulfate reduction, Autotrophic denitrification and Nitrification Integrated process). The experimental system consisted of an up-flow anaerobic bed for sulfate reduction, an anoxic filter for autotrophic denitrification using dissolved sulfide produced in the up-flow anaerobic bed and an aerobic filter for nitrification. The system successfully operated for more than 180 days with an overall organic carbon removal efficiency of 95%, in which, 82% removal was contributed by the up-flow anaerobic bed operating at a HRT of 6 h, and 13% removal by the anoxic filter. An average COD removed /sulfate removed ratio was found to be 0.76 gCOD/gSO(4) or 2.28 COD/gSO(4)-S further confirming that the organic removal was mainly achieved by the sulfate reduction. In terms of nitrogen removal efficiency, the SANI system was found sensitive to the recirculation rate between the anoxic filter and the aerobic filter. A recirculation rate of 3Q was found to be optimal for achieving 74% of the total nitrogen removal. It was confirmed that the autotrophic denitrification was a major contributor to the total nitrogen removal in the SANI system. Sulfur balance analysis indicated that both the accumulation of elementary sulfur in the biomass and the loss of hydrogen sulfide were trivial. During the entire operation period (330 days to date), no sludge was wasted from any reactors in this system. This was further confirmed by the biomass balance simulation results that low biomass yields of sulfate reducing bacteria, autotrophic denitrifiers and nitrifiers contribute to the zero excess sludge discharge. PMID- 19474483 TI - Quantitative fluorescent in-situ hybridization: a hypothesized competition mode between two dominant bacteria groups in hydrogen-producing anaerobic sludge processes. AB - Two hydrogen-producing continuous flow stirred tank reactors (CSTRs) fed respectively with glucose and sucrose were investigated by polymerase chain reaction-denatured gradient gel electrophoresis (PCR-DGGE) and fluorescent in situ hybridization (FISH). The substrate was fed in a continuous mode decreased from hydraulic retention time (HRT) 10 hours to 6, 5, 4, 3, and 2 hours. Quantitative fluorescent in-situ hybridization (FISH) observations further demonstrated that two morphotypes of bacteria dominated both microbial communities. One was long rod bacteria which can be targeted either by Chis150 probe designed to hybridize the gram positive low G + C bacteria or the specific oligonucleotide probe Lg10-6. The probe Lg10-6, affiliated with Clostridium pasteurianum, was designed and then checked with other reference organisms. The other type, unknown group, which cannot be detected by Chis150 was curved rod bacteria. Notably, the population ratios of the two predominant groups reflected the different operational performance of the two reactors, such as hydrogen producing rates, substrate turnover rates and metabolites compositions. Therefore, a competition mode of the two dominant bacteria groups was hypothesized. In the study, 16S rRNA-based gene library of hydrogen-producing microbial communities was established. The efficiency of hydrogen yields was correlated with substrates (glucose or sucrose), HRT, metabolites compositions (acetate, propionate, butyrate and ethanol), thermal pre-treatment (seed biomass was heated at 100 degrees C for 45 minutes), and microbial communities in the bioreactor, not sludge sources (municipal sewage sludge, alcohol-processing sludge, or bean-processing sludge). The designed specific oligonucleotide probe Lg10-6 also provides us a useful and fast molecular tool to screen hydrogen producing microbial communities in the future research. PMID- 19474484 TI - Material flow analysis as a tool for sustainable sanitation planning in developing countries: case study of Arba Minch, Ethiopia. AB - Material Flow Analysis is a method that can be used to assess sanitation systems with regard to their environmental impacts. Modelling water and nutrients flows of the urban water, wastewater and waste system can highlight risks for environmental pollution and can help evaluating the potential for linking sanitation with resource recovery and agricultural production. This study presents the results of an analysis of nitrogen and phosphorus flows of Arba Minch town in South Ethiopia. The current situation is modelled and possible scenarios for upgrading the town's sanitation system are assessed. Two different scenarios for nutrient recovery are analysed. Scenario one includes co-composting municipal organic waste with faecal sludge from pit latrines and septic tanks as well as the use of compost in agriculture. The second scenario based on urine diversion toilets includes application of urine as fertiliser and composting of faecal matter. In order to allow for variations in the rate of adoption, the model can simulate varying degrees of technology implementation. Thus, the impact of a step-wise or successive approach can be illustrated. The results show that significant amounts of plant nutrients can be provided by both options, co composting and urine diversion. PMID- 19474485 TI - Exploring sustainable urban water governance: a case study of institutional capacity. AB - The sustainable urban water management system is likely to be characterised by complex and flexible governance arrangements, increased inter-organisational interaction and wide stakeholder participation, which contrasts significantly with the traditional approach. Recently there has been significant financial investment in urban water reform, however the reforms have not been as successful as anticipated and numerous institutional barriers remain. Understanding and assessing institutional capacity is central to addressing institutional impediments. Institutional capacity comprises individual, intra- and inter organisational and external rules and incentives capacities. This paper reports on the first case study of a social research project that aims to develop an institutional capacity assessment framework. Empirical data from semi-structured interviews with 59 water industry experts in Sydney, Australia, and a broad literature survey were used. The key capacity attributes identified could form the basis of an institutional capacity assessment tool and reveal common and differing attributes across stakeholder groups which provide insight into stakeholder relations. Synthesis of the results revealed that intra- and inter organisational capacities were facing particular challenges and should be explicitly addressed in reform, policy and capacity development initiatives. PMID- 19474486 TI - Incidence of multiple antibiotic resistant Gram-negative bacteria isolated from surface and underground water sources in south western region of Nigeria. AB - In most rural and urban settlements, particularly in Nigeria, wells, spring, streams or rivers and lakes serves as major sources of water supply for drinking and other domestic purposes. Unfortunately, many of the available water sources are not potable without some form of treatment which is seldom available in most settings. The use of untreated surface water sources for drinking and for domestic purposes remains a major threat to public health as these could serve as reservoirs the for transfer of antibiotic resistant pathogens. The incidence of resistant bacteria isolated from surface and underground water in six rural settlements in Ekiti State Nigeria was thus investigated. Gram-negative bacteria were isolated from wells, streams and boreholes in six rural settlements in Ekiti State Nigeria between January and April, 2006 and the prevalence of organisms exhibiting multiple antibiotic resistance to tetracycline, amoxicillin, cotrimoxazole, nitofurantoin, gentamicin, nalidixic acid and ofloxacin was observed. Gram-negative bacterial isolates comprised Escherichia coli (22.7%), Enterobacter aerogenes (2.5%), Salmonella spp. (13.3%), Shigella spp. (19.3%), Proteus spp. (18.5%), Klebsiella spp. (19.3%) and Pseudomonas aeruginosa (4.2%). Over 10% of the bacteria were resistant to four or more antibiotic. Antibiotic resistance was highest in members of the genera Enterobacter, Pseudomonas, and Proteus. Given the prevalence of appalling sanitary facilities and inappropriate public antibiotic use, the possibility of antibiotic resistance selection, faecal dissemination and subsequent contamination of local water sources available for rural residents of the developing world is highlighted. The implication for clinical practice of infections caused by antibiotic resistant strains especially among immunodeficient individuals is also discussed. PMID- 19474487 TI - In situ nutrient removal from aquaculture wastewater by aquatic vegetable Ipomoea aquatica on floating beds. AB - Nutrient-rich effluents caused rising concern due to eutrophication of aquatic environment by utilization of a large amount of formula feed. Nutrient removal and water quality were investigated by planting aquatic vegetable on artificial beds in 36-m(2) concrete fishponds. After treatment of 120 days, 30.6% of total nitrogen (TN) and 18.2% of total phosphorus (TP) were removed from the total input nutrients by 6-m(2) aquatic vegetable Ipomoea aquatica. The concentrations of TN, TP, chemical oxygen demand (COD) and chlorophyll a in planted ponds were significantly lower than those in non-planted ponds (P<0.05). Transparency of water in planted ponds was much higher than that of control ponds. No significant differences in the concentration of total ammonia nitrogen (TAN), nitrate nitrogen (NO(3) (-)-N) and nitrite nitrogen (NO(2) (-)-N) were found between planted and non-planted ponds. These results suggested that planting aquatic vegetable with one-sixth covered area of the fishponds could efficiently remove nutrient and improve water quality. PMID- 19474488 TI - Effects of different quinoid redox mediators on the simultaneous removal of p cresol and sulphide in a denitrifying process. AB - The catalytic effects of different quinoid redox mediators (RM) on the simultaneous removal of sulphide and p-cresol in a denitrifying process were evaluated in batch studies. 2-Hydroxy-1,4-naphthoquinone (LAW) and anthraquinone 2,6-disulphonate (AQDS) did not significantly affect the sulphide oxidation rate, which, in contrast, was increased 14% in the presence of 1,2-naphthoquinone-4 sulphonate (NQS). The input of NQS on the oxidation of sulphide was also favourably reflected in a 13% higher sulphate production. All RM promoted a higher (up to 34% compared to the control lacking RM) degree of mineralization of p-cresol. LAW also supported a 47% higher denitrifying yield (Y(N2)), compared to the control lacking quinones. Nevertheless, AQDS and NQS decreased the Y(N2) by 12-13%. Our results suggest that a proper scrutiny should be conducted before deciding the sort of quinone to be applied in denitrifying processes. The heterogeneous effects observed also advise to consider both the respiratory rates and the yields as important parameters for deciphering the impact of RM on denitrifying processes. PMID- 19474489 TI - Effects of natural organic matter removal by integrated processes: alum coagulation and PAC-adsorption. AB - This paper presents the results of bench-scale research into the efficiency of NOM removal by integrated processes-alum coagulation and PAC-adsorption. Experiments were conducted using riverine water samples (collected from the Odra River, Poland) and commercial powdered activated carbon. It has been shown that a PAC-enhanced coagulation process reduces the coagulant dose required and increases the process efficiency at the same time. For example, a coagulant dose of 2.0 mgAl/L and a PAC dose of 5 mg/L have produced results comparable to those of a coagulation process with no adsorbent aid but with a coagulant dose increased by 54%. The coagulation-adsorption tests were carried out at a pH of 6.0, which was lower than the pH(IEP) of the adsorbent. This procedure yielded a high extent of DOC and UV-254 removal, at 90% and 77%, respectively. The drop observed in the SUVA value after the process implied a decrease in reactive DOC forms and consequently a diminished risk that disinfection by-products might form. HPSEC analyses made it possible to describe the changes in the molecular weight distribution for the organic substances persisting in the water both after coagulation and after PAC-aided coagulation, and to evaluate their propensity to removal by the two methods. The coagulation process was effective as far as the removal of high-molecular-weight fractions is concerned. An increase in the removal of the low molecular weight NOM was achieved when the PAC-adsorption process had been combined with coagulation. PMID- 19474490 TI - Extraction of extracellular polymeric substances from the acidophilic bacterium Acidiphilium 3.2Sup(5). AB - Extraction of extracellular polymeric substances (EPS) from Acidiphilium 3.2Sup(5) was investigated using five methods: EDTA, NaOH, ion exchange resin, heating and centrifugation. The bacterium studied presents promising application in microbial fuel cells (MFCs). The degree of cellular lysis provoked by each method was determined by UV-visible spectroscopy of cultures before and after EPS extraction. In addition, two electron microscopy techniques (TEM and SEM) were employed to determine the degree of attachment and the growth of the biofilm overtime on two solid supports: carbon fibre cloth and graphite rods. The main constituents of the EPS extracted by all methods were proteins and carbohydrates, as confirmed by FT-IR analysis, showing the major presence of carboxylic, hydroxylic and amino groups. The greater extractions of EPS were obtained using EDTA. This method also produced a less degree of cellular lysis. Furthermore, both the amount and the chemical composition of EPS strongly depended on the extraction method used. PMID- 19474491 TI - Evidence of specialized bromate-reducing bacteria in a hollow fiber membrane biofilm reactor. AB - Bromate is a carcinogenic disinfection by-product formed from bromide during ozonation or advanced oxidation. We previously observed bromate reduction in a hydrogen-based, denitrifying hollow fiber membrane biofilm reactor (MBfR). In this research, we investigated the potential existence of specialized bromate reducing bacteria. Using denaturing gradient gel electrophoresis (DGGE), we compared the microbial ecology of two denitrifying MBfRs, one amended with nitrate as the electron acceptor and the other with nitrate plus bromate. The DGGE results showed that bromate exerted a selective pressure for a putative, specialized bromate-reducing bacterium, which developed a strong presence only in the reactor with bromate. To gain further insight into the capabilities of specialized, bromate-reducing bacteria, we explored bromate reduction in a control MBfR without any primary electron acceptors. A grown biofilm in the control MBfR reduced bromate without previous exposure, but the rate of reduction decreased over time, especially after perturbations resulting in biomass loss. The decrease in bromate reduction may have been the result of the toxic effects of bromate. We also used batch tests of the perchlorate-reducing pure culture, Dechloromonas sp. PC1 to test bromate reduction and growth. Bromate was reduced without measurable growth. Based on these results, we speculate bromate's selective pressure for the putative, specialized BRB observed in the DGGE was not growth related, but possibly based on resistance to bromate toxicity. PMID- 19474492 TI - Anaerobic filter for polishing effluent of UASB reactor treating strong sewage at 23 degrees C. AB - Anaerobic filter (AF) was used for polishing effluent of UASB reactor treating strong sewage at an average water temperature of 23 degrees C. The UASB-AF system was operated with sludge discharge taking place only from the AF reactor. It was hypothesized that better removal of suspended COD (COD(ss)) fraction from the system can be achieved by increasing sludge discharge frequency from the AF reactor. For this purpose, sludge discharge frequencies of once, twice and thrice per day from the AF reactor were investigated. Results showed that average total COD (COD(tot)) removal efficiency of the system increased from 62% when sludge was discharged once per day from the AF reactor up to 67% when sludge was discharged twice and thrice per day. However, the increase in COD(tot) removal was not due to increased removal of COD(ss) fraction; but mainly due to development of an active biomass on the filter media, which increased removal efficiency of soluble COD fraction. The AF reactor had also an evidence of pathogens reduction. The AF reactor achieved 1-2 log reduction in Fecal Coliform counts. PMID- 19474493 TI - Ureolytic phosphate precipitation from anaerobic effluents. AB - In this work, the elimination of phosphate from industrial anaerobic effluents was evaluated at lab-scale. For that purpose, the ureolytic method previously developed for the precipitation of Ca(2 + ) from wastewater as calcite was adapted for the precipitation of phosphate as struvite. In the first part of the study, computer simulations using MAPLE and PHREEQC were performed to model phosphate precipitation from wastewater as struvite. The results obtained showed that relative high concentrations of ammonium and magnesium are needed to precipitate phosphate as struvite. The total molar concentrations ratio of Mg(2 + ):PO(4) (3-)-P:NH(4) (+) required to decrease PO(4) (3-)-P concentrations from 20 to 6 mg PO(4) (3-)-P/l at pH 8.4-8.5 was estimated on 4.6:1:8. In the second part of the study, lab-scale experiments with either synthetic wastewater or the anaerobic effluent from a vegetable processing industry were carried out in batch and continuous mode. Overall, the continuous operation at a hydraulic retention time (HRT) of 2.4 h and an added molar concentration [Mg(2 + )]:[PO(4) (3-) P]:[NH(4) (+)] ratio of 1.6:1:2.3 resulted in a constant pH value in the reactor (around 8.5) and an efficient phosphate removal (>90%) to residual levels of 1-2 mg PO(4) (3-)-P/l. Different operational conditions, such as the initial phosphate concentration, HRT and the use of CaCl(2) or MgO instead of MgCl(2), were analysed and the performance of the reactor was satisfactory under a broad range of them. Yet, overall, optimal results (higher phosphate removal) were obtained with MgCl(2). PMID- 19474494 TI - Fractionation of natural organic matter in the Nile River: implications for treated water quality. AB - Recent sampling projects in greater Cairo, Egypt have indicated the presence of trihalomethanes and other chlorine disinfection by-products (DBPs) in the public water supply at levels that are periodically in excess of regulatory limits. Therefore, hydrophobic-hydrophilic fractionation of natural organic matter (NOM) was performed for raw Nile River water samples in order to identify the organic fractions that most readily react with chlorine to produce DBPs. Averages of five events over a 13-month period revealed that the hydrophilic neutral fraction made the highest contribution (35%) to the dissolved organic carbon (DOC), followed by hydrophobic (29%), transphilic (23%), and hydrophilic charged (13%) fractions. Relative contribution of NOM fractions to DBP formation was measured according to the trihalomethane formation potential (THMFP) test. Although the transphilic fraction was only the third highest contributor to DOC, on average it constituted the major contribution to THMFP (38%) followed by the hydrophobic fraction (31%). This finding was corroborated by the results of two events in which samples were collected in both Cairo and Luxor (750 km upstream). The transphilic fraction also yielded the best correlation between percent contributions to THMFP versus DOC. PMID- 19474495 TI - Achieving integrated urban water management: planning top-down or bottom-up? AB - Integrated Urban Water Management (IUWM) acknowledges a broad range of environmental and socio-economic outcomes but the link between design intentions and operational performance is not always clear. This may be due in part to a lack of shared principles that remove bias and inconsistency in assessing the operational performance of IUWM. This paper investigates the possibility of developing shared principles through examination of shared objectives and shared indicators within two logical and integrated frameworks for urban residential developments that aspire for IUWM and sustainable development. The framework method was applied using very different approaches-one a top-down urban planning process, the other a bottom-up community consultation process. Both frameworks highlight the extent to which IUWM is part of a broad social and environmental system. Core environmental performance objectives and indicators were very similar, highlighting the potential to develop shared principles in reporting and benchmarking the environmental performance of neighbourhood developments. Socio economic indicators were highly variable due to process and likely contextual differences, thus it is unclear if the influence of IUWM on these variables can transcend the social context unless the practice of urban water management can expand its core responsibility beyond "hard" physical infrastructure. PMID- 19474496 TI - Aggregate characterisation by using the FlocFormer system to improve sludge dewatering. AB - In this paper, the influence of the polymer-induced flocculation on undigested sludge dewatering is investigated by image analysis. The mixing of flocculants in a so-called rapid-mixer and the subsequent forming of aggregates is carried out by the FlocFormer system, a new sludge conditioning system. For the mechanical dewatering a decanter device is used. To evaluate the efficiency of the dewatering process, the total solid content (TS) of the dewatered sludge is analysed. The results of this study show that this type of flocculation represents an alternative to improve sludge dewatering of undigested sludge. Compared with the standard conditioning (T-mixer), the FlocFormer leads to a better improvement (1.37 to 3.46%-points) in terms of TS while the rapid-mixer improves the dewatering efficiency only by 0.50 to 1.73%-points. Additionally, by using the FlocFormer conditioning, an optimal polymer dose of 5 g/kg TS has been detected. By increasing the polymer consumption (4-20% above the optimal dose) the dewatering efficiency remains practically constant (TS approximately 26.5%). PMID- 19474497 TI - Treatment of olive-mill wastewater from a two-phase process by chemical oxidation on an industrial scale. AB - This study offers a solution for reducing the environmental effect of wastewaters generated by the olive-oil industry. Olive-oil companies produce variable quantities of wastewaters, which require treatment for disposal or reuse. Today, regulations are becoming increasingly strict regarding the parameters measured in these effluents. In Spain, the resolution by the president of the Hydrographical Confederation of the Guadalquivir on water use 2004 set parameter limits as follows: pH = 6.0-9.0, total suspended solid = 500 mg/L; and COD and BOD(5) (20)=1,500 mg O(2)/L. For the year 2006, maximum values for COD and BOD(5) (20) were fixed at 1,000 mg O(2)/L. To solve this problem, a study has been made to derive irrigation water from the above-mentioned effluents through chemical oxidation based on the Fenton's process. This would be first step towards using a closed-circuit system in olive-oil mills to treat and reuse effluents. PMID- 19474498 TI - Application of image analysis in activated sludge to evaluate correlations between settleability and features of flocs and filamentous species. AB - Digital image analysis is a useful tool to estimate some morphological parameters of flocs and filamentous species in activated sludge wastewater treatment processes. In this work we found the correlation between some morphological parameters and sludge volume index (SVI). The sludge was taken from a pilot-scale activated sludge plant, owned by ENEA, located side stream to the Trebbo di Reno (Bologna, Italy) municipal WWTP and fed by domestic wastewater. In order to use image analysis, we developed a correct method to acquire digital microbiological observations and to obtain images altogether representative of the sludge properties. We identified and assessed the parameters needed to estimate the settleability of the sludge and evaluated the morphological filamentous features. It is known that several conditions (i.e. low F/M, nutrient deficiency, low dissolved oxygen) select specific filamentous species and their excessive growth decrease floc-forming/filaments ratio, correspond to the worse settleability properties; we found a relationship between the relative abundance of filamentous species and SVI. We also evaluated the fractal dimension parameter (FD) and determined a threshold value useful to distinguish between the "weak" and "firm" floc and we found a correlation between FD and SVI. PMID- 19474499 TI - Reversing clogging in subsurface-flow constructed wetlands by hydrogen peroxide treatment: two case studies. AB - One of the most frequently encountered operational problems in subsurface-flow constructed wetlands is clogging. Traditionally, the restoration procedure is to remove the clogged gravel or sand and replace it with clean material. This method, while effective, is costly and may require sections of the facility to be taken offline for extended periods of time. Another common remediation strategy is to have a resting period for each wetland cell, although this is not an option for very small systems which often consist of only one treatment cell. Recently, a more radical approach has been tested on a number of lab-scale and pilot-scale setups which consists of an aggressive oxidation of organic matter by means of hydrogen peroxide (H(2)O(2)). Results indicate that after treatment, clogging was substantially reduced and that H(2)O(2) did not appear to have a long-term negative effect on plants and biofilms. The outcomes of two full-scale tests are discussed in this paper. PMID- 19474500 TI - Selective separation of phosphate and fluoride from semiconductor wastewater. AB - Hydrofluoric acid (HF) and phosphoric acid (H(3)PO(4)) are widely used in semiconductor industry for etching and rinsing purposes. Consequently, significant amount of wastewater containing phosphate and fluoride is generated. Selective separation of phosphate and fluoride from the semiconductor wastewater, containing 936 mg/L of fluoride, 118 mg/L of phosphate, 640 mg/L of sulfate, and 26.7 mg/L of ammonia, was studied. Chemical precipitation and flotation reactions were utilized in the two-stage treatment processes. The first-stage reaction involved the addition of magnesium chloride (MgCl(2)) to induce selective precipitation of magnesium phosphate. The optimal condition was pH 10 and molar ratio, [Mg(2 + )]/[(PO(4) (3-))], of 3:1, and 66.2% of phosphate was removed and recovered as bobierrite (Mg(3)(PO(4))(2).8H(2)O). No reaction was found between MgCl(2) and fluoride. Calcium chloride (CaCl(2)) was used in the second-stage reaction to induce precipitation of calcium fluoride and calcium phosphate. The optimum molar ratio, [Ca(2 + )]/[F(-)], was 0.7 at pH 10, and residual fluoride concentration of 10.7 mg/L and phosphate concentration of lower than 0.5 mg/L was obtained. Thermodynamic equilibrium was modeled with PHREEQC and compared with experimental results. Sodium dodecylsulfate (SDS) was an effective collector for subsequent solid-liquid removal via dispersed air flotation (DiAF). The study demonstrated that phosphate can be selectively recovered from the wastewater. Potential benefits include recovery of phosphate for reuse, lower required dosage of calcium for fluoride removal, and less amount of CaF(2) sludge. PMID- 19474501 TI - Nonylphenol concentration and estrogenic activity in Kaoping River and its tributaries, Taiwan. AB - This study investigated the occurrence of nonylphenol (NP) and 17beta-estradiol equivalent quotient (EEQ) concentrations in Kaoping River and two of its tributaries in Taiwan. During this study 44 water samples were collected from four sampling campaigns. Concentrations of NP in these samples ranged from 0.19 to 183.4 mug/L; EEQ ranged from less than limit of detection (1.41) to 32.2 ng E2/L. NP concentrations in the main watercourse ranged from 0.19 to 9.21 mug/L; EEQ ranged from less than limit of detection to 2.13 ng-E2/L. These values are comparable to most rivers worldwide. The Wulo Creek tributary was polluted by animal waste discharges and the NP concentrations ranged from 0.72 to 6.8 mug/L. The EEQ ranged from 3.86 to 32.2 ng-E2/L. The Niouchou Creek tributary was polluted with domestic wastewater. Concentrations of NP ranged from 8.79 to 183.4 mug/L and EEQ ranged from 2.94 to 27.8 ng-E2/L. These data suggest that both inadequately treated livestock and human wastewater can cause high NP and EEQ concentrations. PMID- 19474502 TI - Computational study on microscale behavior of bubble generated by aeration in a plug-flow aeration tank. AB - The microscale hydrodynamics of bubbles generated by aeration is directly related to the oxygen transfer efficiency and the overall performance of the activated sludge wastewater treatment process. To gain a deeper insight on the microscale phenomena of dispersed bubble occurring in this process, a three-dimensional direct simulation method is developed to study the effects of the liquid cross flow on microscale behavior of bubble generation in a plug-flow aeration tank. The numerical simulations are performed using the level set method coupling with the governing equations of a single fluid with variable properties. The governing equations are solved using the finite-volume technique. The simulation results are validated through comparison with experimental observations. The study indicates that the liquid cross-flow has a strong impact on the bubble generation. Compared to that generated under quiescent liquid conditions, the bubble under liquid cross-flow conditions grows downstream along the tilted axis. The bubble generation time tends to decrease noticeably and the bubble at detachment has significantly smaller size. The bubble size and generation time also increase with the increase of gas velocity. The relation of such results to the oxygen transfer efficiency of the wastewater treatment process is also discussed. PMID- 19474503 TI - Applicability of immobilized wood-rotting fungal biomass for biosorption of basic dye Alcian Blue. AB - In this study potential applicability of immobilised biomass of a wood-rotting dead macro-fungus Fomitopsis carnea are explored for the removal of the basic dye Alcian Blue. Effect of several parameters viz., temperature, pH and salt were studied in batch mode. In view of reutilization of the dye as well as the biosorbent, desorption/regeneration experiments were conducted. Desorption/regeneration studies could also be helpful in determining dye sorption mechanism. Studies indicate that the immobilized biosorbent could remove Alcian Blue efficiently. The experimental equilibrium data were modeled using the Langmuir equation. Dye uptake capacity of the biosorbent was observed to increase with rise in temperature and indicates chemisorption and/or ion exchange. The uptake was 11.1, 13.2, 16.4 and 24.2 mg/g at 10, 20, 30 and 40 degrees C respectively. Higher removal of dye was also observed at higher pH. However, increased salt concentration from 0 mmol/L to 100 mmol/L reduced from 89 to 85%. Desorption of dye could be possible up to 51% using 0.1 M hydrochloric/acetic acids and thus suggests that ion-exchange and chemisorption could be the possible dye sorption mechanism. PMID- 19474504 TI - Evaluation of catalysts and membranes for high yield biohydrogen production via electrohydrogenesis in microbial electrolysis cells (MECs). AB - Publisher's note. We very much regret that in the course of production the correct version of Figure 2 of this article was replaced by a figure from another article. The correct version of Figure 2 is shown below. PMID- 19474505 TI - Overlapping left ventricular restoration. AB - Cardiac transplantation, a final option of treatment for refractory heart failure, has not been a standard procedure in Japan especially, mainly because of the shortage of donors. However, surgical methods to restore native heart function, such as surgical ventricular restoration (SVR), are often effective for these cases. The Dor procedure has been used for ischemic cardiomyopathy cases presenting with broad akinetic segments. This is a fine method to exclude the scarred septum and to reduce the intraventricular cavity by encircling purse string suture, but it may produce a postoperative spherical ventricular shape as a result of endoventricular patch repair. Also, partial left ventriculectomy is not recommended for non-ischemic dilated cardiomyopathy cases for now. A modification of these SVR and surgical approaches to functional mitral regurgitation has been named "overlapping ventriculoplasty" without endoventricular patch and resection of viable cardiac muscle, and "mitral complex reconstruction", which consists of mitral annuloplasty, papillary muscle approximation, and suspension. Although the long-term prognosis of these procedures is undetermined, they could be an important option, at least as an alternative bridge to transplantation. This review will describe the concepts and some technical aspects of these procedures for the end-stage heart. PMID- 19474506 TI - Surgical treatment for heart failure: left ventricular restoration for cardiomyopathy. AB - Congestive heart failure has become a major problem and the only surgical treatment for end-stage heart failure caused by dilated cardiomyopathy (DCM) had been heart transplantation. However, because of the shortage of donors, several procedures for non-transplant surgery have been developed. Published literature on left ventricular (LV) restoration was searched to review the new surgical procedures for treating patients with ischemic or non-ischemic DCM. LV restoration was initiated in the 1980s for repairing LV aneurysm. In the 1990s several surgical procedures were introduced for treating DCM, and the new evolving surgical treatment plays an important role in the management of DCM in the 21st century. PMID- 19474507 TI - Management of severe heart failure. AB - Patients admitted to the hospital with heart failure (HF) include those with new onset of acute HF and those with acute exacerbation of chronic HF (CHF). In therapy for new-onset acute HF associated with acute myocardial infarction, therapy to inhibit left ventricular (LV) remodeling in the convalescent phase is required in addition to that needed to overcome the acute phase. Hitherto, CHF therapy was aimed at improving LV contractability, whereas more recently the aim has shifted to resting the heart. Most patients with HF should be routinely managed with a combination of 3 types of drugs: a diuretic; an angiotensin converting enzyme inhibitor and/or an angiotensin II receptor blocker; and a beta blocker. The administration of beta-blockers is of particular importance. For HF unresponsive to medical therapy, non-pharmacological therapies are considered. When a HF patient fails to respond to all available therapies, heart transplantation becomes necessary. Of the 1,000 HF patients admitted to our hospital, two cases received heart transplants. 11 cases were indicated for heart transplantation but died before registration. It should be remembered that although in Japan the possibility of receiving a heart transplant is very low, it is by no means entirely impossible. PMID- 19474508 TI - Cardiac resynchronization therapy with and without implantable cardioverter defibrillator. AB - Cardiac resynchronization therapy (CRT) is recommended to reduce morbidity and mortality in patients with New York Heart Association class III/IV, who are symptomatic despite optimal medical therapy, and who had a reduced left ventricle (LV) ejection fraction and electrical dyssynchrony. The effects of CRT are reflected mainly by the degree and location of dyssynchrony and by working in insertion of optimal LV lead site. Echocardiography and Doppler echocardiography are considered to be good tools to measure LV dyssynchrony directly. However, the large randomized trials have shown that no single echocardiographic measure of dyssynchrony is recommended to improve patient selection for CRT beyond current guidelines. There were several unsolved issues on CRT, such as patient selection, electrical or electromechanical dyssynchrony criteria to patients for CRT, indication of patients with a narrow or slightly prolonged QRS width, indication of patients with atrial fibrillation, and indication of patients with mild heart failure or asymptomatic LV dysfunction, and device selection; CRT alone (CRT-P) or CRT in combination with implantable cardioverter therapy (CRT-D). This review paper summarized the concept of therapy, the current evidence regarding the indications, effectiveness and safety of CRT-P and CRT-D in patients with LV dysfunction, and unsolved issues. PMID- 19474509 TI - Cardiac regenerative medicine: cellular therapy and tissue engineering. AB - Interest in regenerative medicine has grown worldwide, not only in academic circles, but also in the mass media. Cardiac disease is a leading cause of death, and many more randomized controlled trials investigating the use of regenerative therapy have been reported for the heart than for other organs. This review discusses the candidates for donor cells to be used in cell transplantation and the mechanisms for improving injured heart function. PMID- 19474510 TI - Surgical treatment of ischemic heart failure: the Dor procedure. AB - Despite the improvements in the treatment of myocardial infarction that have translated into a decline in mortality rates, the incidence of heart failure has increased and, because of the limited number of cardiac donors, non-transplant heart surgery has developed in the past 10 years. Surgical ventricular reconstruction was launched by Dor and defined as endoventricular circular patch plasty repair. It represents a relatively novel surgical approach aiming to restore (bring back to normal) the dilated, distorted left ventricular (LV) cavity in order to improve function. The term ;surgical ventricular reconstruction/restoration' includes operative methods that reduce LV volume and restore its shape. The concept of reducing wall stress through surgical restoration of chamber size and geometry remains the guiding principle behind this innovative technique. Results from different Institutions are uniform and show an improvement in cardiac and clinical status and in survival. The present review will approach the rationale to re-shape the heart on the basis of pathophysiology and cardiac architecture, and will describe the efficacy of the Dor procedure in ischemic dilated cardiomyopathy, as well as some technical aspects and patient selection pathway. PMID- 19474511 TI - Oncogene associated cDNA microarray analysis shows PRAME gene expression is a marker for response to anthracycline containing chemotherapy in patients with diffuse large B-cell lymphoma. AB - CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) therapy achieves a response in more than 60% patients with diffuse large B-cell lymphomas (DLBCLs). However, DLBCL shows a heterogeneous response to chemotherapy, and some patients are refractory to CHOP therapy. This difference in response to therapy is most likely due to differences in biological characteristics. We used cDNA microarray analysis to identify genes differentially expressed in anthracycline containing chemotherapy-resistant DLBCLs (7 patients) compared with anthracycline containing chemotherapy-sensitive DLBCLs (6 patients). Nine genes on the cDNA chip showed increased expression in anthracycline containing chemotherapy resistant patients. We chose the preferentially expressed antigen of melanoma (PRAME) gene because it showed the highest expression in anthracycline containing chemotherapy-resistant DLBCLs on the cDNA chip, and it has been linked to prognosis of hematological malignancies. We also examined the relationship between PRAME gene expression and progression-free survival (PFS) in 45 patients with DLBCL. The progression-free survival of PRAME-positive patients (n=12) was significantly worse than that of PRAME-negative patients (n=33) (p=0.0373). Our results therefore indicate that PRAME expression in DLBCL correlates with response to anthracycline containing chemotherapy. PMID- 19474512 TI - Attenuated antibody reaction for the primary antigen but not for the recall antigen of influenza vaccination in patients with non-Hodgkin B-cell lymphoma after the administration of rituximab-CHOP. AB - To assess the humoral response to the influenza vaccine in patients undergoing R CHOP therapy (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and predonisolone) for non-Hodgkin lymphoma (NHL), the anti-hemagglutinin (HA) titer in 7 NHL patients undergoing therapy was compared with those in 10 control group subjects in the 2005/2006 season. Four weeks after vaccination, the HA titers against the influenza type A H1N1 and type B antigens, the same antigens that had been used in the previous seasons, were elevated in all patients treated with R-CHOP. In contrast, there was no increase in the geometric mean titer for type A H3N2 antigen, which was newly included in 2005/2006 season, in the patients treated with R-CHOP, while there was a significant increase in the 10 control subjects (p = 0.014). This study showed that vaccination against influenza virus generated an appreciable humoral response to recall antigens in NHL patients treated with R-CHOP therapy, but not to the primary antigen. PMID- 19474513 TI - Histological variety of localized lymphoid hyperplasia of the large intestine: histopathological, immunohistochemical and genotypic findings of 16 cases. AB - Previous reports emphasized that localized lymphoid hyperplasia (LLH) of the large intestine is usually histologically characterized by large lymphoid follicles with striking enlarged germinal centers, and a narrow surrounding mantle zone and marginal zone (MZ). To clarify the histological varieties of LLH of the large intestine, 16 such cases have been studied. The present study demonstrated histological diversity of the LLH of the large intestine including (i) reactive follicular hyperplasia (RFH) (n=8), (ii) RFH with progressive transformation of the germinal center (PTGC) (n=3), (iii) RFH with MZ hyperplasia (n=3) and (iv) RFH with PTGC and MZ hyperplasia (n=2). Overall histomorphological findings of the present series appear quite different from previous descriptions of LLH of the large intestine. The present study showed histological variety of the LLH of the large intestine. Moreover, LLH of the large intestine should be differentiated from extranodal marginal zone B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma as well as follicular lymphoma. Immunohistological studies demonstrated the reactive nature of all 16 lesions. However, three cases showing RFH demonstrated immunoglobulin heavy chain gene rearrangement by polymerase chain reaction study in 12 cases examined. It remains unclear whether these three cases showing RFH could be a sign of the prelymphomatous stage (incipient follicular lymphoma) or representing merely an exaggeration of normal B-cell clonal response in the germinal centers. PMID- 19474514 TI - Immunohistochemical discrimination of plasmacytoid dendritic cells from myeloid dendritic cells in human pathological tissues. AB - Until now, no method has been available to discriminate mature plasmacytoid DC (pDC) from myeloid DC (mDC) immunohistochemically. In this study, we report that these DC-subsets can be distinguished in routine pathological sections. Immature and mature monocyte-derived DCs (MoDCs) were S100 calcium binding protein B (S100B)+, while pDCs generated from pDC-precursors were S100B-. In contrast, both mature MoDC and pDC were fascin+. Epidermal Langerhans cells (LCs) were S100B+/fascin-. Although the majority of DCs were S100B+/fascin+ in the dermis with nonspecific inflammation, dermal DCs were mostly S100B-/fascin+ in psoriasis vulgaris, in which type I interferon secreted by pDC-precursors is thought to play a major role. S100B+/fascin+ DCs were accumulated in the superficial lymph node (LN), while they were scarce in the deep LN. In the superficial LN with dermatopathic lymphadenitis, a large number of S100B+/fascin+ DCs were accumulated in the T-zones, where numerous LC-derived DCs are accumulated. In contrast, almost all DCs were S100B-/fascin+ in the superficial LN with Kikuchi's lymphadenitis, in which numerous pDC-precursors are known to be present. In contrast to the superficial LN, the deep LN contained numerous S100B-/fascin+ DCs and a few S100B+ DCs. Thus, the distributions of S100B+ DC or S100B-/fascin+ DC correspond to the putative distribution of mDC or mature pDC, respectively. PMID- 19474515 TI - Secondary malignant fibrous histiocytoma following refractory langerhans cell histiocytosis. AB - We describe a rare case of secondary malignant fibrous histiocytoma (MFH) following Langerhans cell histiocytosis (LCH). A 23-year-old Japanese male exhibited systemic lymphadenopathy, multiple lung tumors, and osteolytic changes in bilateral iliac bones in 1989. A biopsy specimen from the left iliac bone revealed an infiltration of S-100 protein-positive histiocyte-like cells intermingled with eosinophils, which confirmed the diagnosis of eosinophilic granuloma, a type of LCH. Although the patient was treated with prednisolone initially, the disease did not respond well and progressed gradually over time. The patient subsequently received multiple courses of chemotherapy and immunosuppressive therapy with many kinds of anticancer agents for 6 years. He also received radiotherapy totaling 136.8 Gy for lung tumors and osteolytic lesions of the pelvis. In 1997, because of the LCH refractoriness, biopsy was performed again from the right inguinal lymph node. Microscopic examinations demonstrated a mixture of spindle-shaped cells and histiocyte-like cells, which appeared to be in a storiform pattern. The tumor cells were immunohistologically positive for CD68 and vimentin, but negative for CD1a and S-100 protein. Therefore, the patient was diagnosed with MFH. Although chemotherapy was continued, the patient died of pneumonia during the neutropenic period following chemotherapy. Autopsy revealed systemic invasion of MFH and dissemination of mucormycosis. LCH was not detected histologically in any tissues. PMID- 19474516 TI - Grade I lymphomatoid granulomatosis with increased uptake of [18F] fluorodeoxyglucose in positron emission tomography: a case report. AB - There are several reports describing [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) findings in patients with lymphomatoid granulomatosis (LYG). We report a case of grade I LYG that showed increased uptake of FDG. The patient was a 63-year-old Japanese male who underwent an FDG-PET/computed tomography (CT) scan in screening for a malignant lesion. Increased uptake of FDG [maximum standard uptake value (SUV(max)), 3.7] was observed in the right hilar region in FDG-PET and enhanced CT revealed a round, abnormal mass that also showed increased FDG uptake. The patient had no previous symptoms. A tumor biopsy was performed and the histological diagnosis was grade I LYG. Therefore, increased SUV(max) in FDG-PET might be useful for diagnosing of LYG. PMID- 19474517 TI - Epstein-Barr virus associated post-transplant Hodgkin lymphoma in an adult patient after cord blood stem cell transplantation for acute lymphoblastic leukemia. AB - Post-transplant lymphoproliferative disorder (PTLD) is one of the most important complications of solid organ transplantation or hematopoietic stem cell transplantation. Most PTLDs are associated with Epstein-Barr virus (EBV) infection. Although post-transplant Hodgkin lymphoma (HL) is included in PTLD, there have been no studies in the literature on adult cases of post-transplant HL after cord blood stem cell transplantation (CBSCT). This is due to the fact that EBV infection of cord blood cells usually does not occur, and EBV-infected lymphocytes of the recipient should be eradicated by preconditioning therapy. We report a 26-year-old woman case of post-transplant HL, which occurred after CBSCT for relapsed acute lymphoblastic leukemia. Three years and eight months after CBSCT, the enlarged cervical lymph node was histologically diagnosed as EBV associated post-transplant HL, which showed immunophenotypes of classical HL and latency type II EBV infection. She underwent chemotherapy, and has survived 4 years and 6 months after CBSCT. Differential diagnosis of post-transplant HL with good prognosis and HL-like PTLD with aggressive behavior is important, and immunohistochemical methods were useful and essential for it. The source of EBV associated HL in this case will be discussed. PMID- 19474518 TI - Cyclin D1 protein overexpression in extramedullary plasmacytoma: a clinicopathologic study of 11 cases. PMID- 19474519 TI - Mutation analysis of MEN1, HRPT2, CASR, CDKN1B, and AIP genes in primary hyperparathyroidism patients with features of genetic predisposition. AB - OBJECTIVE: Primary hyperparathyroidism (PHPT), a common endocrine condition, is usually caused by sporadically occurring parathyroid adenoma. A subset of patients carry germline mutations in genes such as MEN1 (multiple endocrine neoplasia type 1), HRPT2 (hyperparathyroidism 2), and CASR (calcium-sensing receptor) predisposing to syndromic forms of PHPT or familial isolated hyperparathyroidism (FIHP). Recently, germline mutations in two novel genes AIP (aryl hydrocarbon receptor-interacting protein) and CDKN1B (cyclin-dependent kinase inhibitor 1B) have been found to be associated with endocrine tumors. The purpose of this study was to evaluate the role of MEN1, HRPT2, CASR, AIP, and CDKN1B genes in PHPT patients with clinical features suggestive of genetic predisposition. PATIENTS AND DESIGN: Medical records of patients treated for PHPT from 1974 to 2001 at Oulu University Hospital were reviewed. Patients with multiglandular or recurrent/persistent disease, other MEN1- related manifestations, aged 40 yr or younger at onset or with a family history of PHPT/MEN1-related tumor were invited to the study. Twenty patients with previously diagnosed MEN1 were excluded. Participants were interviewed and blood samples obtained for biochemical screening and mutation analysis of MEN1, HRPT2, CASR, AIP, and CDKN1B. RESULTS: Of the 56 invited patients, 29 took part in the study. One patient was found to carry the c. 1356_1367del12 MEN1 founder mutation. Mutations in other genes were not detected. CONCLUSIONS: Apart from MEN1, mutations in other genes predisposing to PHPT seem to be rare or non existing in Northern Finnish PHPT patients. No evidence was found for a role of AIP or CDKN1B in PHPT predisposition. PMID- 19474520 TI - UCP1 -3826 AG+GG genotypes, adiponectin, and leptin/adiponectin ratio in severe obesity. AB - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78 40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy. PMID- 19474522 TI - Novel mutation of CYP21A2 gene (N387K) affecting a non-conserved amino acid residue in exon 9. PMID- 19474521 TI - Effects of moderate-severe exercise on blood glucose in Type 1 diabetic adolescents treated with insulin pump or glargine insulin. AB - BACKGROUND: Few papers focus on exercise-related blood glucose (BG) in patients on continuous sc insulin infusion (CSII) or multiple daily injections (MDI) with glargine. AIM: The main objective was to evaluate the degree of glycemic control in Type 1 diabetes mellitus adolescents on CSII doing physical activity with pump switched on or off. These findings were also compared with a small group of patients on MDI with glargine. SUBJECTS AND METHODS: Eight patients on CSII (basal rate continued or turned off in alternating sessions) and 5 on MDI joined 4 sessions of moderate-severe exercise. RESULTS: Post-exercise BG significantly increased with the pump off and was unchanged/decreased with the pump on and MDI groups vs baseline. The hypoglycemia rate was not different among the 3 groups at any time. Pump on: hypoglycemias more frequent both at bedtime (p=0.031) and at awakening (p<0.001) than before dinner and at awakening than at bed-time (p=0.044). Pump off: hypoglycemias more frequent both at bed-time (p=0.010) and at awakening (p=0.031) than before dinner. MDI: no differences. CONCLUSIONS: Glargine is safe and reducing the pre-lunch insulin is unnecessary. Subjects on insulin pump should not stop the basal rate. If they stop the pump, some actions are advisable: pre-exercise insulin bolus, pre-sleeping snack rich in carbohydrates, slight reduction of the overnight basal rate. On the other hand, if the basal rate is unmodified, the ingestion of sugary drinks during the exercise, the reduction of the overnight basal rate, a reduction of the pre dinner insulin bolus and/or a pre-sleeping snack should be considered. PMID- 19474523 TI - Serum amyloid A attenuates cellular insulin sensitivity by increasing JNK activity in 3T3-L1 adipocytes. AB - A permanent increase in acute-phase serum amyloid A (A-SAA) level is observed in obesity and insulin resistance. Recently, A-SAA has been shown to correlate with obesity and insulin resistance in human. However, what triggers A-SAA up regulation is poorly understood, and the mechanism of elevated A-SAA to insulin resistance has not been elucidated. In this study, we used two cellular models of insulin resistance, one induced by treatment with tumor necrosis factor-alpha (TNF-alpha) and the other with the glucocorticoid dexamethasone. Gene expression analysis showed that SAA3 mRNA levels were increased in both models of insulin resistance, and ELISA showed that A-SAA levels were increased in both models too. To assess the potential impact of A-SAA on insulin resistance, we treated 3T3-L1 adipocytes with recombinant human SAA (Rh-SAA) and found that Rh-SAA attenuated cellular insulin sensitivity, up-regulated the level of phosphor-JNK, and down regulated the level of phosphotyrosine-IRS-1 and the expression of glucose transporter 4 (GLUT4) in 3T3-L1 adipocytes. Pre-treatment of cells with C-Jun amino-terminal kinases (JNK) inhibitor brought about partial restoration of Rh SAA-induced insulin resistance. In sum, our findings suggest that serum amyloid A might be a marker of insulin resistance, and it might play a major role in the development of obesity-related insulin resistance. Moreover, in our study it has been proved that JNK is indeed a crucial component of the pathway responsible for SAA-induced insulin resistance in 3T3-L1 adipocytes, which suggests that a selective interference with JNK activity might be a useful strategy in the treatment of Type 2 diabetes and other insulin-resistant states. PMID- 19474525 TI - A national study of iodine status in Albania. AB - OBJECTIVE: The aim of the study was to determine the iodine status in Albania following 11 yr of iodine prophylaxis and to evaluate factors influencing the outcome. DESIGN: Eight hundred and forty children, aged 6-13 yr, living in 4 different regions and 365 pregnant women living in the same areas, were enrolled for the study. The prevalence of goiter was assessed by palpation and ultrasound imaging and the urinary iodine and the iodine concentration in the salt of different commercial brands were evaluated. Presence of goiter in the family and their eating habits were also investigated as well as the use of iodized salt in the household. MAIN OUTCOME: In children, the prevalence of goiter was 57.6% by palpation and 24.4% by ultrasound imaging. Median urinary iodine was 86.2 microg/l, with pronounced geographical variations (range 3.52-1079 microg/l). In particular, 29.1% of the children had urinary iodine <50 microg/l and 57.1% <100 microg/l. In pregnant women, the median urinary iodine was 85 microg/l. Median iodine concentration in household iodized salt was 21.2 mg/kg, with 60.3% of the brands being adequately and 39.7% non-adequately iodized. Almost all families (99.6%) claimed to use iodized salt. CONCLUSION: Despite the introduction of iodine prophylaxis, there is still a mild iodine deficiency in Albania, particularly in the inner mountainous areas. PMID- 19474524 TI - Systolic pulmonary artery pressure and echocardiographic measurements in patients with euthyroid Hashimoto's thyroiditis. AB - BACKGROUND: The aim of this study was to investigate systolic pulmonary artery pressure (SPAP) and echocardiographic findings in patients with euthyroid Hashimoto's thyroiditis (HT). METHODS: Thirty (8 male, 22 female, mean age 47.4+/ 10.5 yr) consecutive patients with euthyroid HT and 30 (9 male, 21 female, mean age 46.4+/-10.7 yr) healthy controls were included in the study. Transthoracic echocardiography was performed for all patients and levels of thyroid hormones, thyroid autoantibodies, glucose, insulin, urea, and creatinine were compared. RESULTS: There were no significant differences in sex, age, body mass index, serum free T4, serum TSH, lipid profiles between patients and controls. Mean SPAP in patients with euthyroid HT were significantly higher than in controls (31.6+/ 5.0 vs 25.6+/-4.5 mmHg, p=0.005). Late diastolic transmitral velocity and isovolumic relaxation time were also significantly higher in patients in comparison to controls. In addition, euthyroid HT patients with tricuspid or mitral regurgitation had a higher grade. Correlation between SPAP and antithyroid antibodies and TSH, however, was not significant in this population. CONCLUSIONS: Pulmonary arterial pressure is higher in patients with euthyroid HT. There may be a relationship between elevated pulmonary arterial pressure and autoimmune thyroid disease independent from thyroid function status. However, further investigations are needed to determine the exact mechanism of association between autoimmune thyroid diseases and pulmonary hypertension. PMID- 19474527 TI - WITHDRAWN: SERUM NT-PRO TYPE BRAIN NATRIURETIC PEPTIDE LEVELS IN NEWLY DIAGNOSED ACROMEGALIC PATIENTS. AB - Ahead of Print article withdrawn by publisher. PMID- 19474526 TI - Adiponectin is associated with serum and adipose tissue fatty acid composition in rats. AB - The objective of the present work is to analyse the relationships between changes in adiponectin and fatty acid composition in serum and adipose tissue in rats. Samples from serum and different adipose depots (periovarian, mesenteric and subcutaneous) were obtained from ageing rats (14- and 20-month-old) to determine fatty acid composition (gasliquid chromatography). In serum, insulin (radioimmunoassay) and adiponectin levels (enzyme-linked immunosorbent assay) were also measured, while adiponectin gene expression was analysed (real time qPCR) in all fat depots. There were significant age-related reductions in adipose tissue saturated (SFA) and trans fatty acids and increases in monounsaturated fatty acids in parallel with diminished adiponectin expression in periovarian and mesenteric adipose tissue (p<0.05). Age-independent negative correlations were found between adiponectin gene expression in mesenteric adipose tissue and C12:0, C14:0 and C18:2 trans fatty acids (p<0.05). There was a positive association between serum adiponectin and adipose tissue oleic acid, while palmitoleic acid was negatively associated with adiponectin expression and positively correlated with insulin concentration. For the first time, positive relationships are reported between the proportion of n-6 polyunsaturated fatty acids (PUFA) in adipose tissue and adiponectin concentration and expression. In summary, adiponectin expression and serum levels are associated with fatty acid composition, with SFA, trans and palmitoleic fatty acids appearing as negative markers for adiponectin, and oleic acid and n-6 PUFA as positive ones. In addition, most associations were found in the visceral depots, highlighting the importance of visceral fat in the metabolic status. PMID- 19474529 TI - What is your threshold for evidence to treat? PMID- 19474528 TI - A low reported energy intake is associated with metabolic syndrome. AB - BACKGROUND AND AIMS: Metabolic syndrome (MS) may be associated with the presence of an energy-sparing metabolism that predisposes to the excess accumulation of body fat. This study examined the relationship between reported energy intake and obesity in individuals with and without MS. METHODS AND RESULTS: Ninety consecutive non-diabetic obese subjects were divided into 2 groups based on the presence (MS+: no.=50) or absence (MS-: no.=40) of MS. The study design was cross sectional. The 3-day food record method was used to assess the subjects' usual energy intake and the Diet Readiness Test (DRT) was also administered. Compared to the MS- group, the MS+ group had a significantly higher body weight, body mass index (mean+/-SEM: 39.1+/-1.3 vs 31.5+/-0.9, p<0.001) and fat mass. The absolute energy intake of the MS+ group (8629+/-331 kJ/24h) did not differ from that of the MS- group (8571+/-515 kJ/24h; p=ns). The daily energy intake normalized for the fat-free mass (FFM) size was higher in the MS- group (163+/-8 kJ/kg-FFM x 24h) than in the MS+ group (138+/-4 kJ/kg-FFM x 24h; p<0.03). The DRT test results were similar in both groups except that section 6 (exercise patterns and attitudes) score was lower in the MS+ group (10.0+/-0.5) than in the MS- group (11.9+/-0.5; p<0.01). CONCLUSION: The results of this study support the hypothesis that subjects with MS have an energy-sparing metabolism. PMID- 19474531 TI - More about premedical education. PMID- 19474532 TI - Why it is smart to facilitate faculty members' resilience. PMID- 19474533 TI - Commentary: Granting medical licensure, honoring the Americans with disabilities act, and protecting the public: can we do all three? AB - Physicians suffer from the same illnesses as others do, and some of these illnesses may limit their ability to safely practice medicine. Individuals with of some of these same illnesses may also suffer from denial, blinding them to their limitations. Data support that, while many of these physicians do voluntarily limit their practices or seek help, not all do. Schroeder and colleagues demonstrate in this issue that in their attempts to protect the public, state medical licensing boards may have asked questions prohibited by the Americans with Disabilities Act. They point out an ethical tension between nonmaleficence (protecting the public from harm) and individual autonomy (respecting the rights of each individual physician), amplified by the different approaches lawyers and physicians use to address conflicts. The classic legal approach is adversarial, whereas the classic medical approach is collaborative. Both are valid approaches, but neither works well in tandem with the other. The time has come for all sides of the licensure debate to acknowledge the legitimacy of the others' concerns, to recognize the different approaches they each take, and to work together with others to find a common solution. The solution must allow boards to identify individuals with illnesses that impair their ability to practice safely and that also lead to denial of these very limitations. The solution must respect the autonomy of the individual licensee with a disability who can practice safely with an accommodation and who respects the need for that accommodation. The solution must protect the public. PMID- 19474535 TI - The separate osteopathic medical education pathway: uniquely addressing national needs. Point. PMID- 19474534 TI - Commentary: impaired physicians and the new politics of accountability. AB - Several recent articles, including the one by Schroeder and colleagues in this issue, document violations of the Americans with Disabilities Act (ADA) by state medical boards that ask applicants for initial licensure and relicensure whether they have any history of mental illness. The authors of these articles argue that the boards' violation of the ADA is a disincentive for applicants to seek treatment, especially for depression. This commentary discusses the behavior of the boards, and efforts to address it, in the larger context of what organizations that educate, examine, license, certify, credential, and represent physicians are doing to improve the accountability of members of the profession and, as a result, the quality of their services. PMID- 19474536 TI - The separate osteopathic medical education pathway: isn't it time we got our acts together? Counterpoint. PMID- 19474537 TI - Osteopathic medical graduates in ACGME residencies: a threat to the core philosophy and distinctiveness of osteopathic medicine. Point. PMID- 19474538 TI - Osteopathic medical graduates in ACGME residencies: another way to embrace the osteopathic philosophy. Counterpoint. PMID- 19474539 TI - Foreword: Osteopathic medicine and medical education in the 21st century. PMID- 19474540 TI - The transformation of osteopathic medical education. AB - Osteopathic medical schools and hospital-based postgraduate programs have long constituted small but important sources of physicians and surgeons, particularly for traditionally underserved areas of the United States. Though frequently marginalized in or even left out of standard histories and studies of U.S. medical education, these institutions have become much more difficult to ignore, given the rapid expansion of the number of osteopathic medical students in new and existing colleges and the size of their classes. By 2019, upwards of 25% of all U.S. medical school graduates produced annually will be doctors of osteopathic medicine. The author examines the process through which osteopathy was transformed into osteopathic medicine, how osteopathic medical schools achieved their present status as a significant source of U.S. graduates for residency training, and what challenges osteopathic medical education now faces. PMID- 19474542 TI - The status and future of osteopathic medical education in the United States. AB - Osteopathic medical education (OME) developed during the 20th century into a separate system of training U.S. physicians. Doctors of osteopathic medicine (DOs) were educated in osteopathic medical colleges and residencies in osteopathic hospitals, took separate specialty and licensure examinations, and generally practiced in separate clinical environments from those of MDs. Founded more than 110 years ago in the United States to train osteopaths as an alternative to MD training of that time, by midcentury schools of osteopathy became schools of osteopathic medicine with the adoption of public health and biomedical principles, and osteopaths became osteopathic physicians, achieving full practice rights throughout the country. By 2000 there were 19 osteopathic medical schools, 42,000 practitioners, and a parallel system of osteopathic graduate medical education specialty training. Recently, OME's academic and clinical training environment has changed. Heightened accreditation requirements, curriculum innovations, competency-based standards, evidence-based training, increased research on osteopathic manipulative medicine (a distinctive aspect of OME), and new and expanding colleges have occurred (nine new osteopathic campuses developed between 2000 and 2008 and a 30% increase in the first-year osteopathic medical student class). During recent decades, a movement away from osteopathic medicine's traditionally primary-care-focused and separate training/practice system has occurred. Nearly all osteopathic hospitals closed or were integrated into allopathic hospital systems, student clinical training expanded into venues with MD education programs, fewer DO graduates pursued traditional primary care training, 60% entered training programs of the Accreditation Council for Graduate Medical Education, and DO and MD specialty practice integration became widespread. These developments have triggered a reassessment process for OME and professional organizational leadership. PMID- 19474543 TI - Osteopathic clinical training in three universities. AB - Osteopathic clinical medical education is similar to allopathic medical education in many ways but uniquely different in others. Some of the important differences include an emphasis on primary care, training in osteopathic manipulative medicine, and the reliance on community-based hospitals for clinical training sites.The authors explore the historical roots of osteopathic clinical training, describe the typical osteopathic clinical preparation, and discuss the challenges in delivering this clinical training. They describe the significantly different methods of delivering clinical training in three osteopathic medical schools: a traditional academic medical center, a school utilizing a statewide clinical consortium, and a school that employs a regional campus system.The authors used data from the annual survey of the 20 schools of osteopathic medicine operating in 2005-2006 to describe the typical clinical rotation experience of an osteopathic medical student and analyzed outcome data from the Comprehensive Osteopathic Medical Licensing Exam (COMLEX) Level 2-CE and COMLEX Level 2-PE for each of these three systems of clinical training. The overall success on these examinations by students from all three schools suggests that all three methods of clinical training can be successful. PMID- 19474544 TI - Factors affecting specialty choice among osteopathic medical students. AB - PURPOSE: The availability of primary care directly and favorable affects the health status of local communities. This study shows the predictors and characteristics of osteopathic medical students who chose a primary care specialty (PCS). METHOD: The authors surveyed 2,345 fourth-year osteopathic medical students during 2003-2004. A total of 1,882 (80%) responded. By means of their survey, the authors examined many aspects of the students' experiences and other factors in relation to choice of a PCS versus a nonprimary nonsurgical specialty (NPCS) and compared their findings against findings in the allopathic specialty-choice literature. RESULTS: Dealing with people was favored by those entering a PCS, whereas the NPCS group cited technical skills, prestige and income, and lifestyle as being highly influential. Both PCS and NPCS respondents favored dually accredited programs (American Osteopathic Association Accreditation Council for Graduate Medical Education). Women showed a slightly greater preference for a PCS, whereas men overwhelmingly chose an NPCS. Those who anticipated practicing in cities of fewer than 100,000 citizens tended to choose a PCS. Those individuals choosing a PCS expect their income to be less than those choosing an NPCS. Debt showed a monotonic influence on specialty choice, with respondents who had greater debt favoring NPCSs. CONCLUSIONS: No single factor reliably predicts specialty choice; it is a complex decision-making process. There are modifiable factors (debt) and nonmodifiable factors (gender) that influence specialty choice. The study's findings suggest that positively influencing the modifiable risk factors will increase the probability but not the certainty of osteopathic medical students' choosing a PCS. PMID- 19474545 TI - The poor historian. PMID- 19474546 TI - Accreditation standards of osteopathic and allopathic medical schools: could they affect educational quality? AB - Accreditation of medical schools in the United States is the province of the Liaison Committee on Medical Education (LCME) for MD-granting schools, and the Commission on Osteopathic College Accreditation (COCA) for DO-granting schools. One of the functions of accreditation is to provide medical schools an opportunity for critical self-analysis, which leads to improvement in quality. In some quarters, there are perceptions that the quality of osteopathic education, and therefore the graduates of DO medical schools, are of a lower quality than is the case with MD schools. To examine that assertion, the authors delved into certain aspects of accreditation across the two professions, particularly the structure of the two accrediting bodies, as well as a comparative analysis of certain select accreditation standards, to determine whether these elements demonstrate any differences that could lead to educational quality dissimilarities.The basic structures of the two accrediting bodies are functionally similar except in the way the members are chosen. Also, the LCME has student representation and COCA does not. However, the authors did not think these differences have significant quality implications. In the areas of governance, the major difference is that a for-profit osteopathic school has now been approved, while the relevant LCME standard states that a medical school should be not-for-profit unless there are extraordinary and justifiable circumstances that preclude full compliance with the standard.Relative to academic environment, LCME standards are more expansive, possibly leading to environments where that may enhance student learning. Comparative analysis of several other standards demonstrates some variation, but not enough to conclude that accreditation is a factor in any quality issues across the two professions. PMID- 19474547 TI - Osteopathic postdoctoral training institutions: a decentralized model for facilitating accreditation and program quality. AB - Osteopathic medicine has experienced significant growth in the number of accredited colleges and graduates over the past decade. Anticipating that growth and recognizing a responsibility to provide sufficient opportunities for quality postdoctoral training, the American Osteopathic Association created a national network of educational consortia to meet the needs of those graduates. These osteopathic postdoctoral training institutions (OPTIs) were to provide enhanced capability for the development and accreditation of new programs, quality oversight, and access to academic resources for their members. The plan reached full implementation in 1999 when all graduate training programs were required to become members of one of these consortia. Although several contributing factors can be considered, an increase in the rate at which training programs have obtained approval by the American Osteopathic Association has occurred under the OPTI model. Quality indicators are more elusive. Each OPTI provides peer-driven oversight to curriculum and faculty development and closely monitors outcomes such as in-service examination scores, certification board passage rates, and resident evaluations of programs.The strategy has enabled a much-sought-after transformation in osteopathic graduate medical education that has provided both strength and accountability to the preexisting infrastructure. As a decentralized accreditation model, OPTI is still evolving and warrants continued application and study. PMID- 19474548 TI - The impact of osteopathic physicians' participation in ACGME-accredited postdoctoral programs, 1985-2006. AB - Between 1985 and 2006, the number of osteopathic physicians (DOs) training in Accreditation Council for Graduate Medical Education (ACGME) postdoctoral (i.e., residency and fellowship) programs increased by 5,352 (419%). In 2006, more than two of every three DOs (6,629 of 9,618) in postdoctoral training were in an ACGME program. The integration of osteopathic physicians into these programs was facilitated by several factors. The most important of these was a noted growth in the number and types of ACGME programs and a consistent number of U.S. MD graduates (USMDs) from schools accredited by the Liaison Committee on Medical Education (LCME). From 1985 to 2006, the number of all physicians in ACGME programs, both DO and MD, grew by 30,365 (41%). DOs were most often selected for specialties less populated by USMDs, chiefly family and internal medicine and pediatrics.Growth patterns in LCME medical schools project an increase in the national class size to accommodate 3,400 more students by 2012, a 21% increase. The development of new colleges of osteopathic medicine (COMs) and expansion in existing ones is expected to generate 5,227 first-year students in 2012, an increase of 1,380 students (36%) over 2006 numbers. The overwhelming majority of these anticipated new COM graduates cannot be accommodated in American Osteopathic Association postdoctoral programs because of limited capacity. As these additional LCME graduates move into their postdoctoral training, educational opportunities for DOs are expected to decline and competition is expected to become stiffer. The window of opportunity for DOs in ACGME programs that opened in the last two decades will gradually start to close. PMID- 19474549 TI - The National Osteopathic Research Center at the University of North Texas Health Science Center: inception, growth, and future. AB - The osteopathic profession has long recognized the need to carry out research in order to improve clinical care. Osteopathic physicians have a particular obligation to carry out research in areas, such as osteopathic manipulative medicine (OMM), that are unique to osteopathic medicine. OMM is similar to manual therapy that is performed by other types of practitioners, but it has some distinctive characteristics. Osteopathic doctors also use OMM to treat infectious disease-not just musculoskeletal disorders.In 2001, several osteopathic professional organizations agreed to jointly fund a national osteopathic research center at one of the osteopathic medical colleges. Five osteopathic colleges submitted research proposals in response to a request for applications. The University of North Texas Health Science Center (UNTHSC) was chosen to be the site for the Osteopathic Research Center (ORC) and was funded for four years with $1.1M. Between 2002 and 2007, the ORC received an additional $11M in research support from multiple sources including federal funds. With this support, it has made substantive contributions to science. These include oversight of the recently completed four-year, $1.5M multicenter study on the efficacy of OMM as a treatment for pneumonia in the elderly and a three-year, $1.9M National Institutes of Health-funded developmental research center to perform mechanistic studies of some OMM actions.The authors discuss the long-term costs, benefits, and sustainability of the national ORC at UNTHSC in the contexts of research accomplished, the training of new medical osteopathic researchers, and an effort to develop other successful regional osteopathic research centers. PMID- 19474550 TI - Clinical practice characteristics of osteopathic and allopathic primary care physicians at academic health centers: results from the National Ambulatory Medical Care Survey. AB - PURPOSE: To explore characteristics of patient visits to osteopathic physicians (DOs) and allopathic physicians (MDs) in the provision of ambulatory primary care services at academic health centers (AHCs) relative to non-AHC sites. METHOD: Physicians report patient visits to the National Ambulatory Medical Care Survey (NAMCS). The authors used NAMCS data (2002-2006) to statistically estimate, characterize, and compare patient visits of four physician provider type- and AHC site-specific subgroups: DOs and MDs at non-AHC sites, and DOs and MDs at AHC sites. RESULTS: The 134,369 patient visits reported in the NAMCS database represented 4.57 billion physician office visits after the authors applied patient weights. These visits included 2.03 billion primary care patient visits (205.1 million DO visits and 1.77 billion MD visits at non-AHC sites; 5.8 million DO visits and 52.3 million MD visits at AHC sites). Practicing at an AHC site appeared to change the dynamic of the patient visit to an osteopathic physician. Most notably, these changes involved patient demographics (sex), patient visit context (practice metropolitan statistical area status, patient symptom chronicity, and injury as reason for the visit), and medical management (diagnostic testing, frequency and intensity of ordering drugs, and use of osteopathic manipulative treatment). CONCLUSIONS: Evidence suggests that osteopathic physicians in community, non-AHC settings offer a more distinctive osteopathic approach to primary care than osteopathic physicians at AHC sites, which both indicates a need for further research to explain this phenomenon and has potentially important implications for osteopathic medical education. PMID- 19474551 TI - The hot lights: reflections on graduation. PMID- 19474552 TI - Medicine and the arts. Dr. Joe [excerpts] by Chet Williamson. Commentary. PMID- 19474554 TI - Teaching Advanced Leadership Skills in Community Service (ALSCS) to medical students. AB - Inadequate access to health care, lack of health insurance, and significant health disparities reflect crises in health care affecting all of society. Training U.S. physicians to possess not only clinical expertise but also sufficient leadership skills is essential to solve these problems and to effectively improve health care systems. Few models in the undergraduate medical curriculum exist for teaching students how to combine needed leadership competencies with actual service opportunities.The Advanced Leadership Skills in Community Service (ALSCS) selective developed in response to the shortage of leadership models and leadership training for medical students. The ALSCS selective is designed specifically to increase students' leadership skills, with an emphasis on community service. The selective integrates classroom-based learning, hands-on application of learned skills, and service learning. More than 60 medical students have participated in the selective since inception. Short term outcomes demonstrate an increase in students' self-efficacy around multiple dimensions of leadership skills (e.g., fundraising, networking, motivating others). Students have also successfully completed more than a dozen leadership and community service projects. The selective offers an innovative model of a leadership-skills-based course that can have a positive impact on leadership skill development among medical school students and that can be incorporated into the medical school curriculum. PMID- 19474556 TI - Community-based advocacy training: applying asset-based community development in resident education. AB - Communities and Physicians Together (CPT) at University of California, Davis Health System provides a novel approach to teaching residents to be effective community advocates. Founded in 1999, CPT is a partnership between a pediatric residency program, five community collaboratives located in diverse neighborhoods, and a grassroots child advocacy organization. Using the principles of Asset-Based Community Development, the program emphasizes establishing partnerships with community members and organizations to improve child health and identifies community assets and building capacity. Community members function as the primary faculty for CPT.The authors describe the CPT curriculum, which teaches residents to build partnerships with their assigned community. Residents have three, two-week blocks each year for CPT activities and maintain a longitudinal relationship with their community. In the first year, collaborative coordinators from each community orient residents to their community. Residents identify community assets and perform activities designed to provide them with a community member's perspective. In the second and third years, residents partner with community members and organizations to implement a project to improve the health of children in that community. CPT also provides faculty development to community partners including a workshop on medical culture and resident life. A qualitative evaluation demonstrated residents' attitudes of their role as pediatricians in the community changed with CPT.CPT is unique because it provides a model of service learning that emphasizes identifying and utilizing strengths and building capacity. This approach differs from the traditional medical model, which emphasizes deficits and needs. PMID- 19474557 TI - Accreditation of undergraduate medical education in the Caribbean: report on the Caribbean accreditation authority for education in medicine and other health professions. AB - Medical education in the Caribbean has undergone significant change and growth in the past decades. Currently, approximately 60 medical schools in the Caribbean provide medical training to a combination of domestic and international students. External quality assurance of these institutions has varied in effectiveness and scope throughout the region. The Caribbean Accreditation Authority for Education in Medicine and Other Health Professions (CAAM-HP) was established by governments of the Caribbean Community as a way to fulfill regional and local needs for a governmentally recognized quality assurance agency. To examine efficient and effective options for maintaining and improving established accreditation systems such as CAAM-HP, the Invitational Conference on Accreditation of Medical Education Programs in the Caribbean took place in May 2007 in Jamaica. The conference was hosted by CAAM-HP and the World Federation for Medical Education, with assistance from the Educational Commission for Foreign Medical Graduates. The evaluation and monitoring of undergraduate medical education programs in the Caribbean by a regional accrediting system such as CAAM-HP can help ensure the quality of the education delivered at these diverse institutions. PMID- 19474558 TI - Do state medical board applications violate the americans with disabilities act? AB - PURPOSE: To determine whether medical licensing board application questions about the mental or physical health or substance use history of the applicant violate the Americans with Disabilities Act (ADA) of 1990. METHOD: Content analysis of 51 allopathic licensing applications (50 states and District of Columbia) was performed at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School in 2005. Questions referencing physical or mental health or substance use were identified by a team of physicians and reviewed and categorized based on the ADA and appropriate case law by legal counsel. RESULTS: Of the 51 applications reviewed, 49 (96%) contained questions pertaining to the physical or mental health or substance use history of the applicant. Thirty-four of the 49 (69%) state medical licensing applications contained at least one "likely impermissible" or "impermissible" item based on the ADA and appropriate case law. CONCLUSIONS: Most state medical licensing applications contain questions that ask about the physical or mental health and substance use of physician applicants. Many licensing applications appear to be in violation of the ADA, even 19 years after enactment of the regulation. These questions do not elicit responses by which professional competence can be judged. The presence of these questions on licensing applications may cause physicians to avoid or delay treatment of personal illness. PMID- 19474559 TI - Becoming a team. PMID- 19474560 TI - Beyond cultural competence: critical consciousness, social justice, and multicultural education. AB - In response to the Liaison Committee on Medical Education mandate that medical education must address both the needs of an increasingly diverse society and disparities in health care, medical schools have implemented a wide variety of programs in cultural competency. The authors critically analyze the concept of cultural competency and propose that multicultural education must go beyond the traditional notions of "competency" (i.e., knowledge, skills, and attitudes). It must involve the fostering of a critical awareness--a critical consciousness--of the self, others, and the world and a commitment to addressing issues of societal relevance in health care. They describe critical consciousness and posit that it is different from, albeit complementary to, critical thinking, and suggest that both are essential in the training of physicians. The authors also propose that the object of knowledge involved in critical consciousness and in learning about areas of medicine with social relevance--multicultural education, professionalism, medical ethics, etc.--is fundamentally different from that acquired in the biomedical sciences. They discuss how aspects of multicultural education are addressed at the University of Michigan Medical School. Central to the fostering of critical consciousness are engaging dialogue in a safe environment, a change in the traditional relationship between teachers and students, faculty development, and critical assessment of individual development and programmatic goals. Such an orientation will lead to the training of physicians equally skilled in the biomedical aspects of medicine and in the role medicine plays in ensuring social justice and meeting human needs. PMID- 19474562 TI - MENTOR-VIP: Piloting a global mentoring program for injury and violence prevention. AB - Injuries occur as the result of a confluence of factors: environmental, social, biological, economic, and behavioral. To effectively address the burden of injuries, especially in low- and middle-income countries, a focus is needed on developing the human resource capacity for injury prevention. MENTOR-VIP is a global mentoring program that the authors developed with this need in mind. MENTOR-VIP approaches developing human resources in injury prevention by providing mentoring opportunities for junior professionals involved in its practice, research, and/or programs. MENTOR-VIP entails a 12-month working relationship between junior injury prevention practitioners (mentees) and more experienced individuals in the field (mentors). Its general objective is to improve global human resource capacity to effectively prevent and control injury and violence through the enhanced development of relevant skills. The program is currently in its pilot phase and is nearing the end of its second formal mentoring cycle, which began on September 1, 2008. This article discusses mentoring professionals as a key strategy to developing the human resource component of capacity, and one which complements existing approaches to capacity development. The authors also provide an overview of the rationale, modalities, objectives, and evaluation of MENTOR-VIP. This article highlights the importance of capacity building in the injury prevention field and situates MENTOR-VIP within the larger context of capacity building for global public health. PMID- 19474561 TI - Perspective: A grand challenge to academic medicine: speak out on gay rights. AB - Social responsibility, a dearly held value in the medical community, requires that medicine use its influence to end discrimination and to reduce barriers that affect access to care. Although the gay, lesbian, bisexual, and transgender (GLBT) population has been identified as suffering from health care disparities and oppression, the medical community and its affiliated organizations have done little to lobby in defense of the GLBT population. And with regard to the specific issue of gay marriage, medicine has yet to raise its voice in that debate, even if only to correct unscientific, capricious, and slanderous depictions of GLBT relationships. Closer to home, in medical schools and residencies, GLBT faculty and students are not provided with a safe and equal environment in which to work and learn. No credentialing provisions require residencies and their affiliate hospitals to include GLBT status in their nondiscrimination policies or to offer GLBT faculty and residents equal benefits. There is no assurance that those in power at peer-reviewed journals will use reviewers who are familiar with the research on sexual minorities to review manuscripts on GLBT topics, a situation that likely contributes to the community's status as an understudied population. Medicine cannot fulfill its obligation to GLBT patients, students, and faculty without a considerable and determined commitment to change. Some of the suggested remedies would require amending policy at the level of the Accreditation Council for Graduate Medical Education and the Association of American Medical Colleges. PMID- 19474563 TI - How leaky is the health career pipeline? Minority student achievement in college gateway courses. AB - PURPOSE: To determine whether underrepresented minority (URM) students receive lower grades than do non-URM students in college prehealth gateway courses; the extent to which lower grade performance might be explained by the differences in precollege academic achievement; and whether URM students are less likely than non-URM students to persist in completing at least four gateway courses. METHOD: Administrative data were obtained from six California colleges on 15,000 college students who matriculated in the 1999-2000 or 2000-2001 academic years and enrolled in at least one college course required for application to medical or dental school ("gateway" courses). Students were compared across ethnic groups in gateway course grade performance and persistence in completing at least four gateway courses, using regression methods to control for students' college admission test scores and caliber of high school attended. RESULTS: URM students received significantly lower grades on average in gateway courses than did white students. This gap persisted after adjusting for measures of prior academic performance. However, URM students were nearly as likely as white students to persist in completing at least four gateway courses. After accounting for the lower grades of URM students in their initial classes, URM students were more likely than white students to complete four or more gateway courses. CONCLUSIONS: URM students experienced academic challenges, but many persist in their prehealth courses despite these challenges. Interventions at the college level to support URM student performance in gateway courses are particularly important for increasing the diversity of medical and dental schools. PMID- 19474564 TI - A multimedia educational program that increases science achievement among inner city non-Asian minority middle-school students. AB - PURPOSE: To test the effectiveness of a middle school, multimedia health sciences educational program called HEADS UP in non-Asian-minority (Hispanic and African American), inner-city students. The program designers hope to increase the number of these students entering the health sciences pipeline. The program includes video role-model stories featuring minority scientists and students, hands-on activities, and teacher resources. Collaborators from The University of Texas Health Science Center at Houston, Spring Branch Independent School District, and the Health Museum developed the modules. METHOD: From 2004 to 2007, the authors used a quasi-experimental, two-group pretest/posttest design to assess program effects on students' performance and interest in science, their science self efficacy, their fear of science, and their science-related careers self-efficacy. An independent third party matched the intervention school to a comparison school by test scores, school demographics, and student demographics and then matched pairs of sixth-grade students (N = 428) by fifth-grade science scores, gender, ethnicity, and participation in the free or reduced lunch program. The authors collected data on these students for three years. RESULTS: At eighth grade (2007), the intervention school students scored significantly higher (F = 12.38, P < .001) on the Stanford Achievement Test 10 in science and reported higher interest in science (F = 11.08, P < .001) than their matched, comparison-school pairs. Students in neither group reported an increase in their confidence to choose a science-related career, but students in one high-implementing teacher's class reported decreased fear of science. CONCLUSIONS: HEADS UP shows potential for improving inner-city, non-Asian-minority middle school students' performance and interest in science. PMID- 19474566 TI - AM Last Page: Osteopathic medicine in the U.S.A. PMID- 19474569 TI - Racial differences in knowledge and beliefs about Alzheimer disease. AB - Alzheimer disease (AD) is a growing public health problem that disproportionately affects racial and ethnic minorities, including African Americans. Given that the perceptions of illness can influence response to treatment options and coping with disease burden, we examined differences between African Americans and whites with regard to their attitudes, beliefs, and knowledge about AD. A total of 301 participants (mean age = 57 y; 80% female; 47% African American) were surveyed by telephone, with overrepresentation of caregivers and first-degree relatives of people with AD (62% of sample). After controlling for potentially confounding covariates, the 2 groups differed in terms of the following: (1) their knowledge about the disease (eg, recognizing that AD is not a part of normal aging); (2) concern about AD (eg, worry about developing the disease); (3) beliefs about putative causes of AD (eg, stress); and 4) beliefs about the effectiveness of various options for reducing risk of and treating AD (eg, physical activity). Findings suggest that AD outreach and education efforts may do well to take into account divergent illness perceptions across racial and ethnic groups. Further research is needed to confirm these findings in more representative samples and to identify factors that explain these racial differences. PMID- 19474570 TI - Prevalence and distribution of cognitive impairment no dementia (CIND) among the aged population and the analysis of socio-demographic characteristics: the community-based cross-sectional study. AB - The epidemiology on "cognitive impairment no dementia" (CIND) and its natural history are of great importance for understanding the transition from normal aging to dementia. Epidemiologic studies of CIND, however, are limited in China. The goal of our study was to determine the prevalence and distribution of CIND in the aged population and analyze socio-demographic factors. To accomplish this, we performed cluster random sampling of 6192 people aged over 65 years in Taiyuan, a metropolitan city located in northern China. Socio-demographic factors were surveyed by self-administered questionnaires. Neuropsychologic testing consisting of the Mini-Mental State Examination, Boston Naming Test, Trail Making Tests A and B, Block Design, Rey Auditory Verbal Learning Test, Visual Reproduction, Logical Memory, letter and category fluency, the National Adult Reading Test, the Geriatric Depression Scale, and the "state" section of the State-Trait Anxiety Inventory was also obtained. Pearson chi statistics and odds ratio with 95% confidence intervals were used to identify the relationship between CIND and socio-demographic factors. Logistic regression modeling was undertaken to identify potential risk factors. Results showed that an overall prevalence of CIND was 9.70% (95% confidence intervals: 9.62%-9.77%). Univariate analyses showed that the prevalence of CIND differed significantly according to age, sex, education level, monthly household income, and marital status (P<0.01), but not by occupational achievement (P>0.05). In a multiple logistic regression analysis, age, sex, marital status, educational level, and occupation were significantly associated with increased risk for CIND (P<0.01). This study confirms the high prevalence of CIND among the elderly population of China, similar to previous epidemiologic studies in other countries. Nearly all socio-demographic characteristics are associated with CIND. The putative risk factors identified merit further study. PMID- 19474567 TI - The Alzheimer's Disease Centers' Uniform Data Set (UDS): the neuropsychologic test battery. AB - The neuropsychologic test battery from the Uniform Data Set (UDS) of the Alzheimer's Disease Centers (ADC) program of the National Institute on Aging consists of brief measures of attention, processing speed, executive function, episodic memory, and language. This paper describes development of the battery and preliminary data from the initial UDS evaluation of 3268 clinically cognitively normal men and women collected over the first 24 months of utilization. The subjects represent a sample of community-dwelling, individuals who volunteer for studies of cognitive aging. Subjects were considered "clinically cognitively normal" based on clinical assessment, including the Clinical Dementia Rating scale and the Functional Assessment Questionnaire. The results demonstrate performance on tests sensitive to cognitive aging and to the early stages of Alzheimer disease in a relatively well-educated sample. Regression models investigating the impact of age, education, and sex on test scores indicate that these variables will need to be incorporated in subsequent normative studies. Future plans include: (1) determining the psychometric properties of the battery; (2) establishing normative data, including norms for different ethnic minority groups; and (3) conducting longitudinal studies on cognitively normal subjects, individuals with mild cognitive impairment, and individuals with Alzheimer disease and other forms of dementia. PMID- 19474568 TI - The Spanish translation and adaptation of the Uniform Data Set of the National Institute on Aging Alzheimer's Disease Centers. AB - Researchers from Alzheimer's Disease Centers (ADCs) across the United States with expertise in the assessment of Spanish-speaking elderly collaborated to create the official Spanish version of measures in the Uniform Data Set of the National Institute on Aging Alzheimer's Disease Center Program. The present article describes this project, whose primary goal was to create Spanish instruments with cultural and linguistic equivalence to the English versions. The resulting Spanish versions make provisions for variations among Spanish-speaking groups in the United States of different nationalities, socio-cultural, linguistic, and educational backgrounds. A consensus-based translation and adaptation approach was used, and guiding principles and specific components of this process are summarized. The Spanish translation and adaptation of the Uniform Data Set measures became available online to ADCs in April 2007. Its creation is important, as the resulting effort provides standardized measures for the collection of cross-sectional and longitudinal data on a large cohort of Spanish speaking elders across the country and facilitates collaborative research among ADCs. PMID- 19474572 TI - Verbal repetition in people with mild-to-moderate Alzheimer Disease: a descriptive analysis from the VISTA clinical trial. AB - BACKGROUND: Verbal repetition is a common symptom and target for treatment in Alzheimer disease (AD), yet little is known of its manifestations in the daily lives of patients. Here we characterized the nature of verbal repetition and its correlates. METHODS: This is a qualitative, secondary analysis of video-recorded interviews with 130 community dwelling mild-to-moderate patients with Alzheimer disease and their carers, enrolled in the Video Imaging Synthesis of Treating Alzheimer's disease clinical trial. Narratives about verbal repetition were characterized using a qualitative framework analysis approach. RESULTS: Verbal repetition was reported in 100/130 patients, 57 of whom identified diminished repetition as a desired outcome of treatment. Most patients (76/100) repeated questions (usually about upcoming events); fewer (32/100) patients repeated statements/stories (usually about recent events). Most repetitions occurred within a 2-hour interval (65/100), and for 52/100 patients the problem was consistent (eg, occurred everyday). There were no differences for interval between repetitions by dementia severity, but most patients who repeated statements/stories were mild (27/32). CONCLUSIONS: Verbal repetition is a common problem, and seems especially to be provoked by upcoming events. More frequent repetitions (shorter intervals between each repetition) were associated with goal setting around this problem. PMID- 19474571 TI - High-throughput, fully automated volumetry for prediction of MMSE and CDR decline in mild cognitive impairment. AB - Medial temporal lobe (MTL) atrophy is associated with increased risk for conversion to Alzheimer disease, but manual tracing techniques and even semiautomated techniques for volumetric assessment are not practical in the clinical setting. In addition, most studies that examined MTL atrophy in Alzheimer disease have focused only on the hippocampus. It is unknown the extent to which volumes of amygdala and temporal horn of the lateral ventricle predict subsequent clinical decline. This study examined whether measures of hippocampus, amygdala, and temporal horn volume predict clinical decline over the following 6 month period in patients with mild cognitive impairment (MCI). Fully automated volume measurements were performed in 269 MCI patients. Baseline volumes of the hippocampus, amygdala, and temporal horn were evaluated as predictors of change in Mini-mental State Examination and Clinical Dementia Rating Sum of Boxes over a 6-month interval. Fully automated measurements of baseline hippocampus and amygdala volumes correlated with baseline delayed recall scores. Patients with smaller baseline volumes of the hippocampus and amygdala or larger baseline volumes of the temporal horn had more rapid subsequent clinical decline on Mini mental State Examination and Clinical Dementia Rating Sum of Boxes. Fully automated and rapid measurement of segmental MTL volumes may help clinicians predict clinical decline in MCI patients. PMID- 19474573 TI - Dysphagia in patients with dementia: Alzheimer versus vascular. AB - Patients with dementia develop dysphagia some time during the clinical course of their disease. The aim of this study was to compare the swallowing functions of the 2 most common types of dementia: Alzheimer disease (AD) and vascular dementia (VaD). Videofluoroscopic swallowing studies of the 2 patient groups were analyzed according to various oral, pharyngeal, and laryngeal variables of swallowing. The results indicate that there are some different patterns of swallowing disorders. The AD patients were significantly more impaired in "oral transit delay over 5 seconds" with liquids (chi2=7.065, df=1, P=0.008), whereas the VaD patients showed more deficits in "bolus formation and mastication" of semisolid food (chi2=4.64, df=1, P=0.039), "hyolaryngeal excursion" (chi2=4.102, df=1, P=0.043), "epiglottic inversion" (chi2=4.612, df=1, P=0.032), and "silent aspiration" (chi2=6.258, df=1, P=0.011). These results could indicate that the swallowing disorders of the AD group may result from sensory impairment in relation to dysfunctions in the temporoparietal areas, whereas the swallowing disorders of VaD group may primarily be caused by motor impairments due to disruptions in the corticobulbar tract. This study is noteworthy because it is one of the first attempts to differentiate between the swallowing symptoms of AD and VaD patients. A further study that includes patients with more severe degree of dementia (eg, patients over clinical dementia rating 3) might delineate additional discriminating swallowing patterns between the 2 dementia groups. In addition, a follow-up study exploring various kinematic characteristics of dysphagia would address physiologic issues of swallowing disorders as related to one of the most important clinical variables, laryngeal aspiration in the 2 dementia groups. PMID- 19474575 TI - One-stage repair of aortic coarctation and ascending aortic aneurysm by extra anatomic graft. AB - The best surgical approach for patients presenting with coarctation of the aorta and additional surgical cardiovascular disorders is uncertain. We describe the case of a young man with an aneurysm of the ascending aorta and a bicuspid aortic valve with a moderate insufficiency associated with a coarctation of the aorta. The patient underwent a single-stage procedure where the ascending aorta was replaced, the aortic valve repaired and the coarctation bypassed with an extra anatomic graft. In our opinion, ascending-to-descending extra-anatomic graft is a good solution to treat these complicated cases. PMID- 19474574 TI - Incidence of spontaneous echocontrast, 'sludge' and thrombi before cardioversion in patients with atrial fibrillation: new insights into the role of transesophageal echocardiography. AB - OBJECTIVES: Transesophageal echocardiography (TEE)-guided cardioversion has been demonstrated to be well tolerated in patients with atrial fibrillation. Guidelines do not suggest whether patients with severe spontaneous echocontrast (SEC) and sludge can be safely submitted to cardioversion. In our observational study, we analyzed the prevalence of SEC in patients with atrial fibrillation taking different anticoagulant therapies, the incidence of embolic complications after cardioversion in patients with severe SEC or sludge and the usefulness of TEE in reducing embolic complications in these patients. METHODS: The study population consisted of 1104 patients with atrial fibrillation, candidates for cardioversion and submitted to TEE. They were divided into four groups: effective conventional oral anticoagulation, short-term anticoagulation, subtherapeutic anticoagulation and effective oral anticoagulation for less than 3 weeks for different clinical reasons. Cardioversion was postponed in patients with atrial thrombosis; in the presence of severe SEC, the decision to cardiovert was left to the treating physician. RESULTS: Atrial thrombosis was detected in 65 (5.9%) patients, and SEC was detected in the majority of patients independent of the anticoagulant scheme; in 131 patients, it was severe and, in this group, sludge was identified in 57 patients. Cardioversion was performed in 922 patients and was successful in 849 (including 22 patients with severe SEC and four with sludge) with one minor embolic event. CONCLUSION: SEC and sludge are frequently observed in patients with atrial fibrillation undergoing cardioversion. A TEE approach may prevent the risk of embolic events. In the presence of severe SEC and sludge, treating physicians frequently postpone cardioversion, even though in the patients submitted to cardioversion, no events were observed. PMID- 19474576 TI - Complex clinical case studies in perinatal and neonatal care. PMID- 19474577 TI - Strategies for the rapid adoption of best practices on the labor and delivery unit. PMID- 19474578 TI - Mentoring nurses for the complexities of neonatal care. PMID- 19474579 TI - Central nervous system vulnerabilities in preterm infants, part II. PMID- 19474580 TI - Best practices in perinatal care: maintaining safe and cost-effective staffing models during the current economic downturn. PMID- 19474581 TI - Management of a partial molar pregnancy: a case study report. AB - Partial molar pregnancy with coexisting fetus is a rare complication of pregnancy and carries significant risks to both the mother and the fetus. Maternal risks include abnormal bleeding and the development of preeclampsia. The fetus frequently develops abnormally, often due to abnormal karyotype. This case presents a woman with a partial molar pregnancy with coexisting fetus, including diagnosis, plan of care, and delivery information. PMID- 19474582 TI - Psychiatric disorders in pregnancy. AB - The care and treatment of women with psychiatric disorders in pregnancy is both challenging and complex. The decision to treat or not treat can pose a risk to the mother, the developing fetus or infant and the pregnancy outcome. Treatment options can be both pharmacologic and non-pharmacologic. The risk and benefit of treatment is a shared decision between the woman and her obstetrical and mental health providers. There is no definitive answer to the optimal treatment of psychiatric disorders in pregnancy. The ideal treatment would minimize the risk to the developing fetus and enable the mother to have few or no psychiatric symptoms during pregnancy. PMID- 19474583 TI - Diabetes crisis in pregnancy: a case report. AB - Optimal maternal, fetal, and neonatal outcomes are the goal of care for pregnant women with preexisting diabetes. Women with a long history of poorly managed diabetes begin pregnancy with a deficit that poses additional challenges for the patient and the healthcare team. The following case study presents a woman who had a history of type 1 diabetes that was poorly controlled and experienced an incidence of severe hypoglycemia with serious sequelae. PMID- 19474584 TI - Streptococcal A infection: reemerging and virulent. AB - Streptococcal A infections are reemerging as a dangerous clinical problem. This particular infection is usually a problem for the postpartum mother and not usually associated with fetal or neonatal infections. Maternal morbidity and mortality are overwhelming when compared with other maternal infections. Historically, group A streptococcus was the cause of epidemic postpartum sepsis prior to the advent of proper hand-washing techniques. Currently, transmission can occur directly from a colonized healthcare provider, other patients, or a community-acquired source. The Joint Commission and the International Surviving Sepsis Campaign have placed patient safety and early recognition and treatment of sepsis as major initiatives to improving patient outcomes. PMID- 19474586 TI - "Understanding Adam" multiple reciprocal translocations: complex case presentation. AB - This article presents a case review of a newborn diagnosed with a complex chromosomal rearrangement, as demonstrated through a painted chromosomal analysis. This infant presented with multiple dysmorphology including cutis aplasia, multiple ocular malformations, bilateral cleft lip and palate, and postnatal hydrocephaly. A chromosomal analysis revealed multiple-ways, balanced translocation involving chromosomes 3, 4, 6, 8, and 9. This case study provides a unique opportunity to, in retrospect, trace each malformation exploring the pathophysiology, etiology, and correlating origin with chromosomal variation. Careful review of this case, enhanced by the visually augmented representation of each translocation, will increase understanding of chromosomal anomalies and their implications in embryological development and clinical presentation. PMID- 19474589 TI - Complex case study: nursing care of an infant with restrictive dermopathy. AB - This article is a complex case study of an infant, born at 33 2/7 weeks' gestation, with restrictive dermopathy, who died at 5 weeks of age. The review of perinatal and postnatal courses, as well as the rare disorder of restrictive dermopathy, a lethal genodermatosis laminopathy, is presented. Neonatal problems are identified. These include problems of prematurity, including need for a neutral thermal environment, nutritional support, and sepsis evaluation. Problems related to the diagnosis of restrictive dermopathy include skin abnormalities of mild hydropic appearance and ichthyosis-like exanthem, thrombocytophilia, pain, and respiratory insufficiency that led to death. The specific social issues of a non-English-speaking family from Russia faced with a lethal diagnosis for their infant are discussed. This infant was born in a community hospital with a perinatal center and tertiary-level neonatal intensive care unit and was transferred at 3 weeks of age to a regional pediatric medical center for subspecialist pulmonary, dermatologic, and genetic evaluation, where she died shortly afterward. Finally, recommendations are made for a nursing care plan related to the problems presented in this case. PMID- 19474588 TI - Supporting parents' decision making surrounding the anticipated birth of an extremely premature infant. AB - Parents who are at risk for giving birth to an extremely premature infant, defined as 22 to 25 weeks' gestation, can find themselves faced with urgent treatment decisions for their unborn infant that have life-altering consequences. Despite the recommendation for involving parents in decision making for these infants, there is limited evidence regarding guidelines for involving parents. In this article, we describe a case from a larger collective case study that examines the decision making and the decision support needs of parents regarding life support decisions made over time (prenatally and postnatally) for extremely premature infants from the perceptions of parents, physicians, and nurses. For this case study, we describe decisions that were made during the antenatal hospitalization of the mother whose infant was stillborn, the support the parents received, and advice for healthcare professionals for improving care to families. For this case, the mother and father, a physician, and 2 nurses were interviewed before the birth of the infant. The findings in this case study demonstrate the importance of the nurse being present when information is given to parents, of informing with compassion, and helping parents to understand treatment options and decisions. PMID- 19474590 TI - A Mexican American mother's experience in the neonatal intensive care unit. AB - BACKGROUND: Most parents would agree that the admission of an infant to the neonatal intensive care unit (NICU) is stressful. Existing research is focused on white mothers, with little known about the experiences of Spanish-speaking, Mexican American mothers who have an infant in the NICU. PURPOSE: The purpose of this qualitative case study was to describe the experiences of a Spanish speaking, Mexican American mother whose infant had been in the NICU. METHODS: Qualitative description was used to conduct this study. One Spanish-speaking, Mexican American mother who had an infant in the NICU was recruited through purposive sampling. An in-depth interview was conducted, audio-recorded, and transcribed verbatim. Conventional content analysis was used to analyze the data. FINDINGS: Analysis of the data revealed that the experience of a Spanish speaking, Mexican American mother who had an infant in the NICU was one of uncertainty, involvement, trust, and anticipating discrimination. PMID- 19474591 TI - Pentalogy of Cantrell: reviewing the syndrome with a case report and nursing implications. AB - Pentalogy of Cantrell is a rare syndrome characterized by 5 distinctive anomalies: epigastric omphalocele, sternal cleft, diaphragmatic defect, diaphragmatic pericardial defect, and intracardiac defect. There are limited case reports documented since its first description in 1958 due to either underdocumentation or underrecognition. One possibility for underrecognition is the idea that there can be incomplete expressions of the syndrome, and these cases may be reported as separate diagnoses. This article explores the case of an infant with the prenatal diagnosis of giant omphalocele who was found to have a complete expression of the pentalogy. Infants with diagnoses such as giant omphalocele and diaphragmatic hernia require complex medical and surgical care. Nursing is in the perfect position to provide these infants with safe, quality, and interdisciplinary care and to provide vital, comprehensive teaching to their parents and families. The need for and value of comprehensive follow-up of these infants cannot be expressed enough. PMID- 19474592 TI - Call your friend today. PMID- 19474593 TI - "Where's respiratory?". PMID- 19474599 TI - Managing epistaxis. PMID- 19474600 TI - How do euphorbia plants cause contact dermatitis? PMID- 19474603 TI - Building a solid understanding of mechanical ventilation. PMID- 19474605 TI - Taking a vested interest in a wearable cardioverter defibrillator. PMID- 19474608 TI - The tale of the sale. PMID- 19474606 TI - New drugs 09, part 2. PMID- 19474609 TI - What you need to know about acute chest syndrome. PMID- 19474610 TI - Five tips for climbing out of a rut. PMID- 19474611 TI - Patient education series. Sleep apnea. PMID- 19474612 TI - Can pressure mapping prevent ulcers? PMID- 19474614 TI - Babesiosis: another tick-borne disease. PMID- 19474619 TI - Using technology to reduce medication errors. PMID- 19474620 TI - Cannabinoids: an emerging role in pain management? PMID- 19474621 TI - Acute pancreatitis. PMID- 19474622 TI - No miracle pills just yet. PMID- 19474623 TI - Providing the right level of care. PMID- 19474624 TI - Consensus model for APRN regulation. PMID- 19474625 TI - Symptomatic presentation of renal cell carcinoma in a young adult. PMID- 19474626 TI - Signs of improvement: diabetes update 2009. PMID- 19474628 TI - Hemochromatosis: Pumping too much iron. PMID- 19474629 TI - Pharmacotherapeutic management of osteoprosis and osteopenia. PMID- 19474631 TI - CVD risk. License to screen: a new mobile intervention program. PMID- 19474632 TI - Guide to care for patients: Osteoporosis. PMID- 19474635 TI - RED Alerts! PMID- 19474636 TI - Using the CCMC code of professional conduct as a living document to uphold ethical practice. PMID- 19474637 TI - Building collaborative partnerships in critical care: the RN case manager/social work dyad in critical care. AB - PURPOSE/OBJECTIVES: More than 5 million patients are admitted annually to intensive care units (ICUs) in the United States. As the life expectancy of the population continues to lengthen, we should expect to see a proportionate increase in the burden of acute and chronic illness as well as a rise in the demand for critical care services. The case management dyad team of nurse case manager and social worker enhances and supports the critical care team through the implementation of collaborative interventions that focus upon the (1) minimization of inpatient transitions, (2) reduction of cost by decreasing the length of stay, (3) promotion of patient and family satisfaction through efforts of advocacy, and (4) enhanced discharge planning. PRIMARY PRACTICE SETTING(S): Hospital ICUs. FINDINGS/CONCLUSIONS: In the critical care setting the professional partnership of the RN case manager/masters in social worker (RN/MSW) dyad is a core component in the linkage of the ICU support system and it enhances the functioning of the ICU multidisciplinary team. The efforts of the dyad team are congruent with the goals of patient care, with the desires of the family, and with the mission of the organization. Shared goals and a shared commitment to professional practice provide the essential building blocks of the dyad relationship. The dyad structure presents an opportunity for RN case managers and social workers to integrate their strengths and skills in a collaborative patient centered effort. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The RN/MSW dyad structure as a model for case management practice promotes continuity of care and strengthens professional relationships. The case manager and the social worker have many shared responsibilities; therefore, a partnership that promotes continuous collaboration and communication is essential to the achievement of successful patient care outcomes. The professional partnership that evolves, as depicted by the RN/MSW dyad structure, enhances the organizations' mission to deliver quality patient-centered care. PMID- 19474639 TI - Preventing the preventable: reducing rehospitalizations through coordinated, patient-centered discharge processes. AB - OBJECTIVES: Growing literature suggests that a significant proportion of rehospitalizations could be prevented if systems were put in place aimed at identifying and addressing some of the underlying issues that cause them. This article highlights key risk factors for unplanned rehospitalizations and illustrates a project that has successfully addressed many of the underlying issues that contribute to them. PRIMARY PRACTICE SETTING(S): The study illustrated herein took place at an inner-city academic teaching hospital. FINDINGS/CONCLUSIONS: Proactively identifying patient-, clinician-, and system associated barriers to successful discharge transitions is critical for effective transitions of care for patients leaving the hospital setting. This process represents a culture change, requires a multidisciplinary approach to care, and mandates clear delineation of roles and responsibilities in the process, with ultimate and clear process ownership being defined. With such steps in place in a system of care, it is reasonable to expect a reduction in preventable rehospitalizations. PMID- 19474642 TI - From ethics violation to remediation: a learning experience--and a reminder for all. PMID- 19474641 TI - Reducing unnecessary medicare admissions: a six-state project. AB - PURPOSE/OBJECTIVES: The Centers for Medicare & Medicaid Services funded a project in six western states to decrease the payment error rate in short-stay admissions (< or =2 days) and decrease the number of inpatient discharges for short stays. Seventeen hospitals were recruited to implement the Case Management Assignment Protocol (CMAP), which standardizes the decision-making process at admission, thereby increasing the number of hospitalized patients assigned to the correct status of inpatient or observation. PRIMARY PRACTICE SETTING: Acute care hospitals. FINDINGS/CONCLUSIONS: Based on the decrease in unnecessary admissions and the relationship between use of the protocol and correct admission status, the project demonstrated that the CMAP was effective in ensuring that patients were placed in the appropriate status. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: 1. Case managers can play a key role in correct assignment of patient status through the use of the CMAP. 2. Hospitals that were successful in implementing the protocol had highly involved senior management, stable corporate environments, physician buy-in, physician champions, policies for mandatory use within the facilities, support from all team members, and "out-of-the-box" thinking for case management coverage. 3. Staffs at hospitals that implemented the protocol indicate they are well positioned for the Recovery Audit Contractor program, which began as a 3-year demonstration project and is now being implemented. It will be in place nationally by 2010. PMID- 19474643 TI - Case management--succeeding in uncertain times. PMID- 19474644 TI - Small changes make a big difference, part II. PMID- 19474646 TI - Falling in an aging brain injury population: analysis of a specific fall prevention protocol in a postacute brain injury rehabilitation center. PMID- 19474647 TI - The emotional impact of disability. PMID- 19474648 TI - Additional HIV-1 mutation patterns associated with reduced phenotypic susceptibility to etravirine in clinical samples. AB - We investigated the phenotypic impact of a number of uncommon amino acid substitutions at HIV-1 reverse transcriptase positions 103 and 138, which are not part of the etravirine resistance score and were found in combination with the high-impact mutation K101P. Etravirine phenotypic fold changes were 380-1400 for K101P + E138A/G/Q + K103N/S/T + V179I and 12-130 for K101P + (K103S +/- V179I) in the absence of E138A/G/Q. Although the effect of K103S is unclear, additional position 138 substitutions seem important for etravirine susceptibility. PMID- 19474649 TI - Incident HIV and herpes simplex virus type 2 infection among men in Rakai, Uganda. AB - OBJECTIVE: Herpes simplex virus type 2 (HSV-2) infection is associated with an increased risk for acquiring HIV, but little is known about the temporal sequence of these infections. DESIGN: : Six thousand three hundred ninety-six men were evaluated for serologic HSV-2 and HIV infections and behaviors during a male circumcision trial in Rakai, Uganda. METHODS: HIV and HSV-2 status were determined using enzyme-linked immunosorbent assays and confirmed by HIV-1 and HSV-2 western blots. A Poisson multivariable model was used to estimate adjusted incidence rate ratios of HIV acquisition associated with HSV-2 and other covariates. RESULTS: HIV incidence was 1.09/100 person-years and acquisition was associated with incident HSV-2 infection [adjusted incidence rate ratio (adjIRR) 5.28, 95% confidence interval (CI) 2.79-9.98], chronic HSV-2 infection (adjIRR 2.78, 95% CI 1.64-5.68), genital ulcer disease, urethral discharge, genital washing after intercourse, being unmarried, and being uncircumcised. Sixteen men acquired both HIV and HSV-2 during the trial: four acquired HIV first, three acquired HSV-2 first, and nine acquired both infections in the same follow-up interval. CONCLUSION: The findings suggest that unsafe sex places men at risk of both HIV and HSV-2 infections, and it is unclear whether HSV-2 acquisition is a cofactor for HIV infection or a marker of correlated sexual exposures. This reinforces the need for promotion of safe sex as the primary method of prevention of both viruses. PMID- 19474650 TI - Characterization of virologic failure patients on darunavir/ritonavir in treatment-experienced patients. AB - OBJECTIVE: Characterization of resistance development in virologic failure patients on the protease inhibitor darunavir administered with low-dose ritonavir (DRV/r) in the 48-week analysis of TMC114/r In Treatment-experienced pAtients Naive to lopinavir (TITAN). DESIGN: TITAN is a randomized, controlled, open label, phase III, noninferiority trial comparing the efficacy and safety of DRV/r with that of lopinavir/ritonavir (LPV/r) in HIV-1-infected, treatment experienced, LPV-naive patients. The primary endpoint was the proportion of patients with HIV-1 RNA less than 400 copies/ml at week 48. METHODS: Patients received DRV/r 600/100 mg twice daily (n = 298) or LPV/r 400/100 mg twice daily (n = 297), and an optimized background regimen. Patients who lost or never achieved HIV-1 RNA less than 400 copies/ml after week 16 were considered virologic failure patients. Genotyping and phenotyping were performed. RESULTS: The virologic failure rate in the DRV/r arm (10%, n = 31) was lower than in the LPV/r arm (22%, n = 65). Furthermore, fewer virologic failure patients in the DRV/r arm than in the LPV/r arm developed primary protease inhibitor mutations (6 vs. 20) or nucleoside reverse transcriptase inhibitor resistance-associated mutations (4 vs. 15). In addition, fewer virologic failure patients on DRV/r than on LPV/r lost susceptibility to the protease inhibitor (3 vs. 13) or nucleoside reverse transcriptase inhibitor(s) (3 vs. 14) used in the treatment regimen or to other protease inhibitors. Most DRV/r-treated virologic failure patients retained susceptibility to all protease inhibitors. CONCLUSION: In treatment-experienced, LPV-naive patients, the overall virologic failure rate in the DRV/r arm was low and was associated with limited resistance development. These findings showed that the use of DRV/r in earlier lines of treatment was less likely to lead to cross-resistance to other protease inhibitors compared with LPV/r. PMID- 19474652 TI - The safety of candidate vaginal microbicides since nonoxynol-9: a systematic review of published studies. AB - OBJECTIVE: To gain a greater understanding of published safety data for candidate vaginal microbicides. DESIGN: A systematic review of human safety trials of candidate vaginal microbicides - agents designed to protect women against HIV and other sexually transmitted infections. METHODS: Trials were published in peer reviewed journals, and publication cut-off was August week 4, 2008. Trials of nonoxynol-9 were excluded, as were trials without a control group, trials that enrolled only male participants or reported on the investigation of a product for the treatment of a genital infection. RESULTS: Twenty-one trials of 11 products, involving 1465 women, satisfied review criteria. Most trials reported on genital epithelial findings and urogenital symptoms and a number reported a range of other local and systemic toxicity endpoints. Trials were generally of short duration (2 weeks or less) with small sample sizes. There were few findings of significant difference between women in active and control arms. Among the products assessed in more than one study, there were significantly more genital findings with intact epithelium in recipients of PRO2000 [relative risk (RR) 1.68, 95% confidence interval (CI) 1.08-2.60] and a lower incidence of bacterial vaginosis in dextrin sulphate recipients (RR 0.61, 95% CI 0.42-0.88). CIs were generally very wide, and most studies were unable to exclude differences of a substantial magnitude between treated and control women. CONCLUSION: Larger and longer safety studies are necessary to detect clinically important toxicities, including those that indicate a potential increase in HIV risk, and provide assurance that agents are ready for large-scale effectiveness trials. PMID- 19474651 TI - Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on muscle glucose uptake and visceral fat in HIV-infected patients. AB - OBJECTIVE: To determine the effects of switching from lopinavir/ritonavir (LPV/r) to atazanavir/ritonavir (ATV/r) on muscle glucose uptake, glucose homeostasis, lipids, and body composition. METHODS: Fifteen HIV-infected men and women on a regimen containing LPV/r and with evidence of hyperinsulinemia and/or dyslipidemia were randomized to continue LPV/r or to switch to ATV/r (ATV 300 mg and ritonavir 100 mg daily) for 6 months. The primary endpoint was change in thigh muscle glucose uptake as measured by positron emission tomography. Secondary endpoints included abdominal visceral adipose tissue, fasting lipids, and safety parameters. The difference over time between treatment groups (treatment effect of ATV/r relative to LPV/r) was determined by repeated measures ANCOVA. RESULTS: After 6 months, anterior thigh muscle glucose uptake increased significantly (treatment effect +18.2 +/- 5.9 micromol/kg per min, ATV/r vs. LPV/r, P = 0.035), and visceral adipose tissue area decreased significantly in individuals who switched to ATV/r (treatment effect -31 +/- 11 cm, ATV/r vs. LPV/r, P = 0.047). Switching to ATV/r significantly decreased triglyceride (treatment effect -182 +/- 64 mg/dl, ATV/r vs. LPV/r, P = 0.02) and total cholesterol (treatment effect -23 +/- 8 mg/dl, ATV/r vs. LPV/r, P = 0.01), whereas high-density lipoprotein and low-density lipoprotein did not change significantly. Fasting glucose also decreased significantly following switch to ATV/r (treatment effect -15 +/- 4 mg/dl, ATV/r vs. LPV/r, P = 0.002). CONCLUSION: Switching from LPV/r to ATV/r significantly increases glucose uptake by muscle, decreases abdominal visceral adipose tissue, improves lipid parameters, and decreases fasting glucose over 6 months. PMID- 19474653 TI - Rhabdomyolysis following clarithromycin monotherapy. AB - Macrolide antibiotics inhibit the metabolism of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) that may result in myopathy and rhabdomyolysis. We report the first case of rhabdomyolysis related to the administration of clarithromycin without concurrent use of other medications. Inhibition of cytochrome P450 could be one of the potential causative mechanisms of myopathy in our case. Clinicians should be aware of this potential adverse effect of a widely used drug. PMID- 19474654 TI - Pancreatic head cancer with distant duodenal metastasis: a case report with rare endoscopic presentations. AB - Metastasis to the duodenum from a primary cancer is rare, but direct extension from pancreatic cancer is much more common. Here, we present a case of multiple duodenal metastases of pancreatic head cancer in a 77-year-old woman with upper gastrointestinal bleeding. An upper gastrointestinal endoscopic examination revealed multiple elevated reddish nodules on a normal mucosa background that extended from the superior duodenal angle to the duodenal second portion. Echo guided fine needle aspiration biopsies of the pancreatic head tumor and endoscopic biopsies of the reddish duodenal nodules proved the diagnosis of adenocarcinoma. When such endoscopic morphology is found, especially when the locations are distant from the papillae, metastasis should be considered and multiple biopsies are mandatory. PMID- 19474655 TI - Implications of thromboprophylaxis registry data on clinical practice. AB - Registries provide important real-world information regarding the risk factors for venous thromboembolism (VTE) and the thromboprophylaxis prescribing patterns among patients who may not be represented in randomized clinical trials. Understanding these components may help improve the future management of patients at risk of VTE. In this review, we highlight the differences between patients enrolled in clinical trials and real-world clinical practice and we examine the use of data from VTE registries to determine real-world patient characteristics and prophylaxis practices. Additionally, we discuss the risk factors or comorbidities of VTE in patients, the prevalence of VTE across different patient subgroups, and the VTE prophylaxis patterns in various subgroups, as reported in registries. We propose that data from both registries and randomized clinical trials should be used together when determining the most appropriate management strategy for individual patients. PMID- 19474656 TI - Characteristics of hepatitis C virus coinfection in a human immunodeficiency virus-infected population with lower reported rates of injection drug use. AB - BACKGROUND: Injection drug use (IDU) is considered the major risk factor for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We examined risk factors for HIV/HCV coinfection in a region with a low reported rate of IDU. METHODS: We identified 146 HIV/HCV coinfected patients in Jackson, Mississippi. Medical records were reviewed for demographics, social history, and risk factors for HIV and HCV acquisition. A randomly selected group of HIV monoinfected patients from the same clinic served as a control group. RESULTS: History of IDU (P < 0.0001), crack cocaine use (P < 0.0001), incarceration (P < 0.0001), and syphilis (P < 0.0001) were significantly associated with HCV infection in this cohort of HIV patients. However, the reported rate of IDU (32.5%) is lower than other published HIV/HCV-infected cohorts. CONCLUSIONS: HIV/HCV patients in Mississippi are less likely to report a history of IDU than other coinfected populations, suggesting an alternative means of HCV transmission. Further studies are needed to examine the role of syphilis, crack cocaine use, and incarceration as risk factors for HCV infection in this population of HIV patients. PMID- 19474658 TI - Postoperative hyperglycemia as a predictor of infectious complications after noncardiac surgery. PMID- 19474657 TI - Triple or quadruple tetracycline-based therapies versus standard triple treatment for Helicobacter pylori treatment. AB - BACKGROUND: Our aim was to compare lansoprazole-tetracycline-metranidazole (LTM) as first-line treatment with the classical lansoprazole-amoxicillin clarithromycin (LAC) and bismuth-containing quadruple treatments. PATIENTS AND METHODS: This prospective, single-center, randomized study included 464 consecutive Helicobacter pylori-positive patients with dyspeptic symptoms. A total of 415 patients completed the study. The patients were allocated into 4 study groups using random sampling numbers as follows-LAC group: lansoprazole 30 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days; BLTM group: bismuth subcitrate 300 mg 4 times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg 4 times a day, and metronidazole 500 mg twice daily for 10 days; RBLTM group: ranitidine bismuth citrate 400 mg twice daily, lansoprazole 30 mg twice daily, tetracycline 500 mg 4 times a day, and metronidazole 500 mg twice daily for 10 days; and LTM group: lansoprazole 30 mg twice daily, tetracycline 500 mg 4 times a day, and metronidazole 500 mg twice daily for 10 days. RESULTS: The per protocol H. pylori eradication rate in LAC, BLTM, RBLTM, and LTM groups were 37 of 104 (35.6%), 56 of 102 (54.9%), 67 of 104 (64.4%), and 63 of 105 (60%), respectively. The intention-to-treat eradication rate was 37 of 113 (32.7%) in LAC, 56 of 119 (47.1%) in BLTM, 67 of 117 (57.3%) in RBLTM, and 63 of 115 (54.8%) in LTM group. The BLTM, RBLTM, and LTM treatment groups achieved a significantly better eradication rate than the LAC treatment group (P < 0.001). There was not any significant statistical difference between the groups of BLTM, RBLTM, and LTM. CONCLUSION: LTM treatment group achieved a significantly better eradication rate than the LAC treatment group. The success ratio of LTM therapy is comparable with quadruple bismuth-based treatments. PMID- 19474659 TI - Peculiarities of wernicke encephalopathy after bariatric surgery. PMID- 19474661 TI - Experience with more than 500 minimally invasive hepatic procedures: a serious note of caution. PMID- 19474663 TI - Immuno-nutrition in upper gastrointestinal surgery. PMID- 19474665 TI - Surgeon volume does not predict outcomes in the setting of technical credentialing results from a randomized trial in colon cancer. PMID- 19474668 TI - Should we rely on impact factors? PMID- 19474669 TI - Breast cancer outcomes: the crucial role of the breast surgeon in the era of personal genetics and systems biology. PMID- 19474671 TI - Robot-assisted gastrectomy with lymph node dissection for gastric cancer: lessons learned from an initial 100 consecutive procedures. AB - OBJECTIVE: To evaluate the technical feasibility, effectiveness, and safety of robot-assisted gastrectomy (RAG) with lymphadenectomy, using the da Vinci system through analyses of our initial series of 100 consecutive patients. SUMMARY BACKGROUND DATA: The application of robotic surgery was proven to be one of the best cutting-edge technologies for successful minimally invasive surgery by providing solutions to the many drawbacks of laparoscopic surgery, yet few reports have studied robotic surgery in gastric cancer. METHODS: A review of a prospectively designed database at our institute from July 2005 to October 2007 revealed a series of 100 consecutive RAG patients with a preoperative diagnosis of early gastric cancer. Clinicopathologic characteristics and surgical outcomes were analyzed. RESULTS: All operations were performed successfully without open or laparoscopic conversion. There were 33 total gastrectomies and 67 subtotal gastrectomies with D1+beta or extended lymphadenectomy (D2). The mean total operation time and console time were 231 and 150 minutes, respectively. There were 13 postoperative morbidities and 1 postoperative mortality. The first flatus was noted on postoperative day 2.9, soft diet was started on postoperative day 4.2, and the mean postoperative hospital stay was 7.8 days. Although all patients were diagnosed as early gastric cancer preoperatively, the final pathology report revealed that 19 patients exhibited a depth deeper than T2. The mean number of retrieved lymph nodes was 36.7 (range, 11-83). None of the specimens showed microscopic tumor involvement in the resection line. CONCLUSIONS: This study demonstrated that RAG with lymphadenectomy can be applied safely and effectively for patients with gastric cancer. PMID- 19474672 TI - A "new era" in the treatment of colorectal cancer liver metastasis: the gloves are off! PMID- 19474673 TI - Characteristics of practice among rural and urban general surgeons in North Carolina. AB - OBJECTIVE: To examine variation in the practice patterns of individual general surgeons and how they differ between rural and urban areas of North Carolina. SUMMARY OF BACKGROUND DATA: Traditional physician supply analyses often rely on "head counts" and do not take into account how physicians' practice patterns differ. Practice characteristics including the volume and the breadth of services that a physician provides may be especially important in understanding the supply and distribution of specialists, such as general surgeons. METHODS: Cross sectional study using physician licensure data linked with administrative records on all inpatient hospital discharges and all surgeries performed at freestanding ambulatory surgery centers in North Carolina in 2004. RESULTS: Total procedure volumes varied widely (interquartile range: 356-700). The average general surgeon in a rural county performed 54 different procedures at least once during the year, compared to 59 in counties with small urban areas and 62 in metropolitan counties. The 10 procedures that a general surgeon performed most frequently accounted for 72% of that surgeon's total annual procedures in rural counties, 67% in counties with small urban areas, and 66% in metropolitan counties. These rural metropolitan differences were smaller after controlling for secondary specialty and other surgeon characteristics. CONCLUSIONS: There was significant variation in the volume and scope of procedures that North Carolina general surgeons performed in the year. Many general surgeons in metropolitan areas performed an array of procedures that was broader than those in rural areas. PMID- 19474674 TI - The trauma risk adjustment model: a new model for evaluating trauma care. AB - BACKGROUND DATA: The trauma injury severity score (TRISS) has been used for over 20 years for retrospective risk assessment in trauma populations. The TRISS has serious limitations, which may compromise the validity of trauma care evaluations. OBJECTIVE: To derive and validate a new mortality prediction model, the trauma risk adjustment model (TRAM), and to compare the performance of the TRAM to that of the TRISS in terms of predictive validity and risk adjustment. METHODS: The Quebec Trauma Registry (1998-2005), based on the mandatory participation of 59 designated provincial trauma centers, was used to derive the model. The American National Trauma Data Bank (2000-2005), based on the voluntary participation of any US hospitals treating trauma, was used for the validation phase. Adult patients with blunt trauma respecting at least one of the following criteria were included: hospital stay >2 days, intensive care unit admission, death, or hospital transfer. Hospital mortality was modeled with logistic generalized additive models using cubic smoothing splines to accommodate nonlinear relations to mortality. Predictive validity was assessed with model discrimination and calibration. Risk adjustment was assessed using comparisons of risk-adjusted mortality between hospitals. RESULTS: The TRAM generated an area under the receiving operator curve of 0.944 and a Hosmer-Lemeshow statistic of 42 in the derivation phase. In the validation phase, the TRAM demonstrated better model discrimination and calibration than the TRISS (area under the receiving operator curve = 0.942 and 0.928, P < 0.001; Hosmer-Lemeshow statistics = 127 and 256, respectively). Replacing the TRISS with the TRAM led to a mean change of 28% in hospital risk-adjusted odds ratios of mortality. CONCLUSIONS: Our results suggest that adopting the TRAM could improve the validity of trauma care evaluations and trauma outcome research. PMID- 19474675 TI - Follicular thyroid carcinoma in an iodine-replete endemic goiter region: a prospectively collected, retrospectively analyzed clinical trial. AB - OBJECTIVE: To determine risk factors for presence of lymph node or distant metastases in patients with follicular thyroid cancer (FTC) at the time of diagnosis and whether there is a relationship between the type of tumor invasion and metastases. SUMMARY BACKGROUND DATA: FTC often presents distant metastases at the initial diagnosis. As distant metastases are independent prognostic factors in a patient's survival, determination of clinicopathologic characteristics for patients who are at higher risk for developing metastases is of greater clinical importance. METHODS: The prognostic significance of gender (male vs. female), age (40 mm), number of lesions (uni- vs. multifocality), type of invasion (minimally invasive vs. widely invasive), and oncocytic changes (with vs. without) were analyzed in 207 patients, according to presence of lymph node and distant metastases at the time of initial surgery. According to the type of invasion, the carcinoma-specific survival and the disease-free survival of minimally invasive (MI) and widely invasive (WI) FTC were estimated and compared. RESULTS: None of the 127 patients with MI growth presented with lymph node metastases but 9.4% distant metastases. Overall risk factors for the presence of lymph node metastases at the initial diagnosis were multifocality (P = 0.02) and widely invasion (P = 0.0001) and for distant metastases age >45 years (P = 0.007), tumor size larger than 40 mm (P = 0.03) and widely invasion (P = 0.0001).WI-FTC patients show larger tumors (P = 0.0001), older age (P = 0.0001), and are presented more frequently in recurrent goiter disease (P = 0.0001). The estimated 10 years carcinoma-specific survival and disease-free survival for MI-tumors were significantly better than for WI tumors (P = 0.0001). CONCLUSIONS: Total thyroidectomy is recommended in all patients with FTC because of early distant metastases. Patients with WI-FTC need a more aggressive surgical treatment because of higher tendency for lymph node metastases. MI-FTC has an excellent prognosis with no sign of lymph node metastases, which emphasizes a limited need for nodal surgery. PMID- 19474677 TI - Safety and efficacy of isolated limb infusion with cytotoxic drugs in elderly patients with advanced locoregional melanoma. AB - INTRODUCTION: The treatment of elderly patients with advanced metastatic melanoma confined to a limb remains controversial. Isolated limb infusion (ILI) is an effective minimally invasive alternative to isolated limb perfusion (ILP) and is therefore a potentially valuable therapeutic option for this group. METHODS: From our prospective database 185 patients with advanced metastatic melanoma of the limb treated with a single ILI between 1992 and 2007 were identified. In all patients a cytotoxic combination of melphalan and actinomycin-D was used. RESULTS: Eighty-six patients (46%) were >or=75 years of age (range: 75-93). The patient characteristics in both groups were comparable except that the older group comprised more women (71% vs. 54%; P = 0.02) and had a lower body mass index (median: 24.4 vs. 26.4; P = 0.008). Complete response rates were 34% for those >or=75 years and 41% in the younger group (P = 0.28). There was no difference in limb recurrence free interval after a complete response (median: 24 months for both groups; P = 0.51) or in survival (median: 36 months for <75, 39 months for >or=75; P = 0.36) between both groups. Older patients experienced less limb toxicity after the procedure (Wieberdink grade III/IV toxicity in 36%) compared with younger patients (51%; P = 0.009) while systemic toxicity, complications, and long-term morbidity were similar. CONCLUSIONS: Elderly patients with advanced metastatic melanoma of the limb experience the same or lower toxicity after ILI compared with younger patients while response rates, limb recurrence free interval, survival, and morbidity are similar. ILI is an attractive alternative to the more laborious ILP, especially for older patients. PMID- 19474676 TI - Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. AB - OBJECTIVE: Improved staging systems for malignant peripheral nerve sheath tumor (MPNST) prognostication and management are needed. Consequently, we sought to identify clinical, pathologic, and molecular predictors of outcome in patients with/without neurofibromatosis type 1 (NF-1) associated MPNST. METHODS: MPNST patients treated from 1986 to 2006 (n = 140) were identified; 72 had NF-1 syndrome and 68 did not. A comprehensive database was constructed. Paraffin embedded neurofibroma or MPNST blocks were assembled in a tissue microarray; marker expression was evaluated immunohistochemically. Univariable and multivariable analyses identified independent factors prognostic of local recurrence, distant metastasis, and disease-specific survival (DSS). RESULTS: DSS at 10 years was 31.6% for 87 primary disease patients, 25.9% for 26 recurrent patients, and 7.5% for 27 metastatic patients after median follow up of 91 months. The 5 years DSS for localized tumor patients was 35% for NF-1 patients and 50% for sporadic patients. MPNST >or=10 cm at diagnosis, partial resection, and metastasis development were significant negative predictors of DSS; completely resected tumors that lacked S-100 immunoreactivity had a nearly 5-fold increased risk of developing distant metastasis. Ki67, vascular endothelial growth factor, p53, and pMEK were over-expressed in MPNST compared with benign neurofibromas. Only tumor size and nuclear p53 expression were found to be independent prognosticators for MPNST DSS in a multivariable analysis. CONCLUSIONS: MPSNT is a markedly metastatic and aggressive poor prognosis tumor. Multiple clinical, pathologic, and molecular markers identified in this study, coupled with findings from previous series, should be considered for an improved MPNST staging system useful for prognostic assessment and management decisions. PMID- 19474678 TI - Is completion lymph node dissection needed in case of minimal melanoma metastasis in the sentinel node? AB - OBJECTIVE: The purpose of this study was to evaluate the micromorphometric Starz classification in melanoma patients. SUMMARY BACKGROUND DATA: The micromorphometric Starz-classification suggests that melanoma patients with a sentinel node metastasis invading no more than 0.3 mm (S-I) or 0.31 to 1.0 mm (S II) below the capsular level can be spared further surgery, while invasion of the metastasis of more than 1.0 mm (S-III) implies a need for completion dissection. METHODS: Seventy patients with sentinel node metastases were studied. Twenty patients with an S-I or S-II classification were spared further surgery and 50 S III patients underwent completion dissection. The median follow-up time was 33 months. RESULTS: No lymph node recurrences were detected in the 20 S-I, II patients. Six of the 50 S-III patients (12%) had additional involved nodes in the dissection specimen. In these patients no recurrences developed in the cleared regional basins. Overall 3-year survival was 100% in the S-I, II patients and 80% in the S-III patients (P = 0.04). Three-year disease-free survival rates were 83% and 60%, respectively (P = 0.40). CONCLUSIONS: : This study suggests that further surgery is unnecessary in S-I and S-II patients, while it does seem prudent to carry out completion dissection in S-III patients. The distinct survival difference between the 2 groups of patients suggests that the S-classification also has prognostic implications. PMID- 19474679 TI - Trends in perioperative outcome after hepatic resection: analysis of 1500 consecutive unselected cases over 20 years. AB - OBJECTIVE: To estimate risk factors affecting the early outcome after hepatic resection in a high volume center specialized in hepatobiliary surgery and to analyze the changing of results during 3 different periods of treatment. DESIGN: Retrospective review. PATIENTS: A series of 1500 consecutive patients who underwent hepatic resection. METHODS: Postoperative morbidity and mortality were analyzed in relation to indications for surgery, period of operation, patient characteristics, and intraoperative variables. Patients were classified into 4 groups, according to the indication for surgery: primary liver tumors with cirrhosis (group 1, G1); other liver malignancies (group 2, G2); biliary malignancies (group 3, G3); and benign diseases (group 4, G4). Patients were also divided into 3 groups, according to the year of operation (period 1: June 1985 to October 1993; period 2: November 1993 to September 1999; period 3: October 1999 to September 2007). RESULTS: Overall mortality and morbidity were 3% and 22.5%, respectively. Multivariate analysis revealed that blood transfusions, G1, and additional procedures were associated with an increased risk of postoperative complications, whereas blood transfusions, G1, G3, and extended hepatectomy were associated with an increased risk of postoperative mortality. G1 decreased, whereas G3, extended hepatectomies and additional procedures significantly increased between periods 2 and 3 (P < 0.05). The complication rate was significantly lower in period 2 (18.8%) compared with period 1 (23.8%) and period 3 (24.8%). Similarly, there was a significantly lower mortality rate in period 2 (1.6%) compared with period 1 (3.4%) and period 3 (4%). CONCLUSIONS: Slightly worse short-term outcomes in liver surgery were observed in recent years, with a concomitant increase of the aggressiveness of operative strategies. Nevertheless, the present results still justify an aggressive approach in liver resections. PMID- 19474680 TI - Reconsideration of postoperative oral intake tolerance after pancreaticoduodenectomy: prospective consecutive analysis of delayed gastric emptying according to the ISGPS definition and the amount of dietary intake. AB - OBJECTIVE: A prospective consecutive study was planned to evaluate the postpancreaticoduodenectomy (PD) oral intake tolerance. The occurrence of delayed gastric emptying (DGE), as defined by the International Study Group of Pancreatic Surgery (ISGPS), and the amount of dietary intake were analyzed. The risk factors for low oral intake tolerance were additionally determined. SUMMARY BACKGROUND DATA: The causation of DGE after PD is still unclear. Several possible factors have been discussed, such as reconstruction methods and other complications. However, none of them has followed the definition of ISGPS. METHODS: Between 2003 and 2007, 101 consecutive patients underwent PD-related surgery, and standard operative procedure was performed on 85 patients. Perioperative data were prospectively collected in all patients, and the patient's postoperative dietary intake was recorded for all meals until discharge. As an indicator of early postoperative oral intake tolerance, we added up the dietary intake from postoperative day 1 to 21 and called this value the total amount of dietary intake (TDI). The postoperative outcomes were compared between non-DGE and DGE. The high-low of TDI values was also analyzed. Multivariate analysis for factors associated with the occurrence of DGE and TDI was performed. RESULTS: The occurrence of DGE as defined by ISGPS was 42%. The postoperative outcomes of DGE patients were significantly poor compared with those of non-DGE patients. TDI values were significantly low in DGE patients, and non-DGE patients with low TDI values showed a significantly extended duration of parenteral nutrition and postoperative hospitalization. Operative bleeding (>1,000 mL) and pancreatic fistulas were likely to be associated with DGE occurrence. Gender (women), BMI (>25 kg/m), postoperative intraabdominal infection, and DGE were significantly associated with low TDI values. CONCLUSIONS: The ISGPS definition of DGE seemed feasible for patient management. TDI values provided additional information for analyzing postoperative oral intake tolerance, especially when describing the differences among non-DGE patients. Substantial risk factors for low oral intake tolerance were high BMI, postoperative intraabdominal infection, and DGE. PMID- 19474681 TI - Tobacco-specific carcinogen enhances colon cancer cell migration through alpha7 nicotinic acetylcholine receptor. AB - OBJECTIVE: To study the mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1 butanone (NNK)-enhanced migration of colon cancer cells. BACKGROUND DATA: Long term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco specific carcinogen, NNK, was reported to increase DNA synthesis of colon cancer cells. Since metastasis is the major cause of cancer death, the influence of NNK on the migration of colon cancer cells remains to be determined. METHODS: Receptor for NNK in colon cancer cells was identified by polymerase chain reaction (PCR) and real-time PCR. The influence of NNK on migration of colon cancer cells was evaluated by transwell and wound-healing assay. Receptor mediated migration was studied by both inhibitor and small interfering RNA. RESULTS: alpha7 nicotinic acetylcholine receptor, alpha7-nAChR, was identified in 2 colon cancer cell lines, HT29 and DLD-1. NNK enhanced HT29 cell migration in both transwell and wound-healing assays. NNK also enhanced DLD-1 cell migration in dose dependent manner. We used inhibitor and siRNA to demonstrate that alpha7 nAChR mediated NNK-enhanced colon cancer cell migration and downregulation of E cadherin were involved in NNK-enhanced migration of colon cancer cells. Furthermore, Snail and ZEB1, 2 major transcription repressors of E-cadherin in colon cancers, were induced by NNK treatment. CONCLUSIONS: Tobacco specific carcinogen, NNK, enhanced colon cancer metastasis through alpha7-nAChR and E cadherin--one of the hallmarks of epithelial mesenchymal transition--and its transcription repressors. Therefore, smoking should be avoided in the patients with colorectal cancer. PMID- 19474682 TI - Colorectal resection is associated with persistent proangiogenic plasma protein changes: postoperative plasma stimulates in vitro endothelial cell growth, migration, and invasion. AB - INTRODUCTION: Plasma vascular endothelial growth factor (VEGF) levels are elevated for weeks after minimally invasive colorectal resection (MICR). Decreased plasma angiopoietin-(Ang) 1 and increased Ang-2 levels have been noted on postoperative days (POD) 1 and 3. These proangiogenic changes may stimulate tumor growth postoperatively (postop). This study's purpose was to track plasma VEGF, Ang-1, and Ang-2 levels for 4 to 8 weeks after MICR for cancer and to assess the impact of preoperative (preop) and postop plasma on in vitro endothelial cell (EC) behavior. METHODS: Blood samples from 105 MICR patients were taken preop, on POD 5 and at varying time points for 2 months. Samples from 7 day time blocks after POD 5 were bundled to permit statistical analysis. Plasma protein levels were measured via enzyme-linked immunosorbent assay. In vitro EC branch point formation, EC invasion, and EC migration assays were carried out with preop, POD 7 to 13 and 14 to 20 plasma. The t test and Bonferonni correction was used. RESULTS: VEGF levels were significantly elevated on POD 5 and 7 to 13; lesser increases were noted on POD 14 to 20 and 21 to 27. Ang-2 levels were significantly increased at all time points postop. No significant Ang-1 changes were noted. When compared to preop EC culture results, there was significantly more EC branch point formation, EC invasion, and EC migration assays noted with POD 7 to 13 and POD 14 to 20 plasma. CONCLUSIONS: MICR is associated with proangiogenic plasma changes for 2 to 4 weeks and plasma from POD 7 to 13 and 14 to 20 stimulated EC growth, invasion, and migration. Postop plasma may stimulate the growth of residual tumor. PMID- 19474683 TI - The influence of the number of retrieved lymph nodes on staging and survival in patients with stage II and III rectal cancer undergoing tumor-specific mesorectal excision. AB - OBJECTIVE: This study was designed to determine whether the number of lymph nodes retrieved influence staging and survival in patients with stage II and III rectal cancer that undergo tumor-specific mesorectal excision. SUMMARY BACKGROUND DATA: The prognostic impact of the retrieved nodes has been emphasized in patients with colorectal cancer, but few studies have focused on patients with rectal cancer. METHODS: A total of 900 patients who underwent tumor-specific mesorectal excision with curative intent and adjuvant chemoradiation therapy for stage II and III rectal cancer from January 1989 to December 2006 were analyzed. RESULTS: Cancer specific survival (CSS) of stage II patients with less than 15 nodes (25th percentile) was not different from stage III patients, but CSS was better in stage II patients with more than 15 nodes. When using cutoff values of the 25th and 50th percentiles (22 and 31 nodes), recurrence-free survival (RFS) was statistically different among subgroups of stage II and III patients. In multivariate analysis, stage II disease with less than 15 nodes retrieved was an adverse factor for CSS and RFS. In Kaplan-Meier survival analysis, using cutoff values, the difference for CSS was not significant with 22 and more nodes and the difference for RFS was not observed with 23 and more nodes. CONCLUSIONS: The number of lymph nodes retrieved is closely associated with survival and recurrence in patients with stage II rectal cancer and, for more accurate prognostic stratification, at least 22 and 23 nodes seem to be necessary, respectively, for CSS and for RFS. PMID- 19474684 TI - The more the better?: the impact of surgeon and hospital volume on in-hospital mortality following colorectal resection. AB - OBJECTIVE: To determine the in-hospital mortality rates for patients undergoing colorectal resection for malignant or benign conditions, and to identify risk factors for in-hospital death, particularly the relationships with surgeon and hospital volume. BACKGROUND: Although there is strong evidence that complex cancer operations are best performed at specialized high-volume centers and by high-volume surgeons, the relationship between surgeon and hospital volume and perioperative outcomes is less well defined for more common procedures such as colorectal resections, particularly for benign diseases. METHODS: We obtained data from the Canadian Institute for Health Information Discharge Abstract Database on all adult patients who underwent colorectal resection between April 1, 2005 and March 31, 2006. We performed a logistic regression to identify variables associated with a higher likelihood of in-hospital death. RESULTS: Twenty-one thousand seventy-four patients underwent colorectal resection, with the majority being elective (59.4%). Malignancy represented the most common indication for resection (56.8%), followed by diverticular disease (16.2%) and inflammatory bowel disease (7.1%). The overall in-hospital mortality rate among patients undergoing colorectal resection was 5.3%. Increased age (adjusted Odds Ratio [OR]: 1.97 per 10 years, P < 0.001), urgent operation (OR: 2.63, P < 0.001), indication for resection (P < 0.001), nature of the surgery (P < 0.001), and several comorbidities were all independently associated with an increased risk of death. Surgeons with higher volumes of colorectal resections achieved significantly lower mortality rates (OR: 0.92 per 20 cases/y, P = 0.003), corresponding to an adjusted mortality rate of 5.6% for surgeons in the bottom decile (1 case per year) compared with 4.5% for surgeons in the top decile (greater than 43 cases per year). Hospital volume was not associated with mortality (OR: 1.00 per 10 cases, P = 0.504). CONCLUSIONS: This large, population based study suggests that surgeons who perform high volumes of colorectal resections achieve lower in-hospital mortality rates than surgeons with low volumes, whereas the hospital volume does not influence mortality. PMID- 19474686 TI - Limited gastrectomy with dissection of sentinel node stations for early gastric cancer with negative sentinel node biopsy. AB - OBJECTIVE: To evaluate the early results of sentinel node (SN)-navigated limited surgery for early gastric cancer. SUMMARY BACKGROUND DATA: False-negative results of SN biopsy cannot be ignored in gastric cancer surgery. Previous studies suggest that dissection of lymph node stations where SNs belong (SN stations) may minimize the possibility of leaving metastasis behind in SN-navigated surgery. METHODS: Patients with T1N0M0 gastric cancer <4 cm were informed about the SN navigated limited surgery from 2003 to 2008. SNs were identified using radioisotope and dye methods. When the SN biopsy by frozen section was negative, limited gastrectomy with dissection of SN stations was performed. Patients with SN stations limited to either the lesser or greater curvature underwent a wedge resection unless it would cause a strong deformity of the stomach. A sleeve gastrectomy was performed in other cases. RESULTS: Six of the 60 enrolled patients chose a standard gastrectomy. Sixteen patients were excluded after laparotomy due to a T2-T3 tumor or tumor location. Three patients with positive SN biopsy underwent D2 gastrectomy, and 35 with negative SN biopsy underwent limited gastrectomy with dissection of SN stations; wedge resection in 8 and sleeve gastrectomy in 27. There were no operative mortalities or morbidities. All patients undergoing the limited surgery had no lymph node metastasis by postoperative pathology, and survived without any recurrence. The average area of the resected stomach for limited surgery was significantly smaller than that for standard procedures (92 +/- 50 vs. 189 +/- 64 cm, P < 0.001). CONCLUSIONS: SN navigated limited gastrectomy with dissection of SN stations for T1N0M0 gastric cancer was considered safe and acceptable although long-term follow-up is mandatory. PMID- 19474687 TI - The chemokine receptor CCR4 is expressed and associated with a poor prognosis in patients with gastric cancer. AB - OBJECTIVES: There is increasing evidence that chemokines and chemokine receptors are causally involved in the metastasis of cancer. Little is known about the possible role of chemokine receptors in the metastasis of gastric cancer. The aim of this study was to investigate the expression of chemokine receptors and their prognostic role in patients with gastric cancer. METHODS: We screened the expression of CCR and CXCR chemokine receptors in 12 gastric cancer cell lines using the semi-quantitative RT-PCR. The expression of CCR4, one of the most commonly expressed chemokines, was confirmed using Western blot and flow cytometry analysis of 8 gastric cancer cell lines. The function of CCR4 was examined using migration and proliferation assays. Then the migratory response of CCR4 was blocked using blocking antibodies. Finally, the clinical significance of the chemokine receptors was explored using tissue microarray methods and immunohistochemical staining of specimens from 753 gastric cancer patients. RESULTS: We found that 6 out of 8 (75.0%) gastric carcinoma cell lines expressed a functional CCR4 for its ligand, chemokine CCL17, as demonstrated by the migration assays, and the migration was inhibited by anti-CCR4 antibodies. The clinical samples evaluated by immunohistochemical assay of tissue microarrays showed that CCR4-positive carcinoma cells were detected in 128 of 753 (17.0%) cases. In addition, there was a significant difference in recurrences between the CCR4-positive and -negative cases (P = 0.009). The patients with CCR4-positive tumors had significantly poorer prognosis than did those with CCR4-negative tumors (5-year survival rate; 71.6% versus 82.5%, respectively, P = 0.008). CONCLUSION: These results suggest that CCR4 and its ligands were associated with increased tumor recurrence and impaired overall survival in patients with gastric cancer. PMID- 19474688 TI - Bisoprolol and fluvastatin for the reduction of perioperative cardiac mortality and myocardial infarction in intermediate-risk patients undergoing noncardiovascular surgery: a randomized controlled trial (DECREASE-IV). AB - OBJECTIVE: This study evaluated the effectiveness and safety of beta-blockers and statins for the prevention of perioperative cardiovascular events in intermediate risk patients undergoing noncardiovascular surgery. SUMMARY BACKGROUND DATA: Beta blockers and statins reduce perioperative cardiac events in high-risk patients undergoing vascular surgery by restoring the myocardial oxygen supply/demand balance and/or stabilizing coronary plaques. However, their effects in intermediate-risk patients remained ill-defined. METHODS: In this randomized open label 2 x 2 factorial design trial 1066 intermediate cardiac risk patients were assigned to bisoprolol, fluvastatin, combination treatment, or control therapy before surgery (median: 34 days). Intermediate risk was defined by an estimated risk of perioperative cardiac death and myocardial infarction (MI) of 1% to 6%, using clinical data and type of surgery. Starting dose of bisoprolol was 2.5 mg daily, titrated to a perioperative heart rate of 50 to 70 beats per minute. Fluvastatin was prescribed in a fixed dose of 80 mg. The primary end point was the composite of 30-day cardiac death and MI. This study is registered in the ISRCTN registry and has the ID number ISRCTN47637497. RESULTS: Patients randomized to bisoprolol (N = 533) had a lower incidence of perioperative cardiac death and nonfatal MI than those randomized to bisoprolol-control (2.1% vs. 6.0% events; hazard ratios: 0.34; 95% confidence intervals: 0.17-0.67; P = 0.002). Patients randomized to fluvastatin experienced a lower incidence of the end point than those randomized to fluvastatin-control therapy (3.2% vs. 4.9% events; hazard ratios: 0.65; 95% confidence intervals: 0.35-1.10), but statistical significance was not reached (P = 0.17). CONCLUSION: Bisoprolol was associated with a significant reduction of 30-day cardiac death and nonfatal MI, while fluvastatin showed a trend for improved outcome. PMID- 19474685 TI - Effect of weight loss by diet or gastric bypass surgery on peptide YY3-36 levels. AB - OBJECTIVE: To examine the effect of an equivalent weight loss, by gastric bypass surgery (GBP) or by diet, on peptide YY3-36 (PYY3-36), ghrelin, and leptin levels and to determine the effect of diabetes status on PYY3-36 levels. SUMMARY BACKGROUND DATA: The increased PYY3-36 levels after GBP may be involved in the magnitude and the sustainability of weight loss after surgery. METHODS: Of the 30 morbidly obese women who participated in the study, 21 had type 2 diabetes mellitus, and were studied before and after equivalent weight loss of 10 kg by either GBP (n = 11) or by diet (n = 10). RESULTS: : PYY3-36 levels were higher in obese diabetic as compared with nondiabetic individuals (64.1 +/- 34.4 pg/mL vs. 39.9 +/- 21.1 pg/mL; P < 0.05). PYY3-36 levels increased markedly in response to oral glucose after GBP (peak: 72.3 +/- 20.5 pg/mL-132.7 +/- 49.7 pg/mL; P < 0.001; AUC0-180: 51.5 +/- 23.3 pg/mL x min-91.1 +/- 32.2 pg/mL x min P < 0.001), but not after diet (peak: 85.5 +/- 51.9 pg/mL-84.8 +/- 41.13 pg/mL; P = NS; AUC0 180: 68.3 +/- 38.5 pg/mL x min-61.1 +/- 42.2 pg/mL.min P = NS). Fasting ghrelin levels increased after diet (425 +/- 91 pg/mL-519 +/- 105 pg/mL; P < 0.05), but did not change after GBP (506 +/- 121 pg/mL-482 +/- 196 pg/mL; P = NS). CONCLUSIONS: Diabetes status seems to be a determinant of PYY3-36 levels. GBP, but not diet-induced weight loss, resulted in markedly increased glucose stimulated PYY3-36 levels. The increase in stimulated PYY3-36 levels after GBP is likely a result of the surgery rather than a secondary outcome of weight loss. Changes in PYY3-36 levels and ghrelin could contribute to the success of GBP in sustaining weight loss. PMID- 19474690 TI - Transvaginal natural orifice translumenal endoscopic surgery cholecystectomy: early evolution of the technique. AB - INTRODUCTION: Initial excitement for Natural Orifice Transluminal Endoscopic Surgery (NOTES) has been partly tempered by the reality that a NOTES procedure without laparoscopic or needleoscopic-assistance has not been performed by most groups. After safely performing laparoscopically-assisted transvaginal cholecystectomy in an IACUC-approved porcine model, we embarked on an IRB approved protocol to ultimately perform a pure NOTES cholecystectomy. MATERIALS AND METHODS: We describe our experience with performing a true NOTES tansvaginal cholecystectomy after safely accomplishing 3 laparoscopically-assisted hybrid NOTES procedures in humans. To overcome the retracting limitations of currently available endoscopes, we used a 5-mm curved or articulating retractor that was placed into the abdomen via a separate colpotomy in the second and third patient. In a fourth patient, pneumoperitoneum to 15 torr was obtained via a transvaginal trocar placed through a colpotomy made under direct vision and endoscopically placed clips were used for both the cystic duct and artery, thus, obviating the need for any transabdominally placed instruments or needles. RESULTS: This patient was the first patient to undergo a completely NOTES cholecystectomy at our institution and to our knowledge in the United States. She was discharged on the day of surgery and has not suffered any complication after 1 month of follow up. CONCLUSION: Pure NOTES transvaginal cholecystectomy without aid of laparoscopic or needleoscopic instruments is feasible and safe in humans. Additional experience with this technique will be required before comparative studies to standard laparoscopy and hybrid techniques are appropriate. PMID- 19474689 TI - Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227). AB - OBJECTIVE: There are 2 main types of access for patients requiring major open, elective abdominal surgery: the midline or the transverse approach. The aim of this study is to compare both approaches by focusing on postoperative pain, complications, and frequency of incisional hernias. SUMMARY BACKGROUND DATA: A recent Cochrane review suggested that transverse incisions may be less painful but incisional hernia rates do not differ. METHODS: Randomized, patient- and observer-blinded, monocentric, equivalence clinical trial. Patients were scheduled for elective primary abdominal incisions. Composite primary end point measured 48 hours after surgery was the total amount of analgesics (piritramide) required in the last 24 hours and pain (Visual Analogue Scale). Secondary end points were early-onset and late complications. This study is registered in the ISRCTN registry and has the ID number ISRCTN60734227. RESULTS: Two hundred patients (101 midline and 99 transverse) were randomized. Both incision types resulted in similar amounts of required analgesics (95% confidence interval [ 0.38; -0.33] was included in the equivalence level). For the Visual Analogue Scale, both the 95% and 90% CI (0-10) were neither within the equivalence levels nor were their differences significant at the 5% level. No relevant differences between midline and transverse incisions were observed for 30-day mortality (2 vs. 2, P = 0.99), mortality after one year (15 vs. 23, P = 0.15), pulmonary complications (13 vs. 17, P = 0.43), median length of hospital stay (11 vs. 12 days, P = 0.08), median time to tolerance of solid food (12 vs. 14 days, P = 0.30), and incisional hernias after one year (13 vs. 8, P = 0.48). More wound infections occurred in the transverse group (15 vs. 5, P = 0.02). CONCLUSION: The decision about the incision should be driven by surgeon preference with respect to the patient's disease and anatomy. PMID- 19474691 TI - Patient safety and surgical training: an unhealthy relationship? PMID- 19474692 TI - Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality. AB - BACKGROUND: : Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been offered in many institutions worldwide since the 1990s. Despite its existence of more than 10 years, this treatment has received heavy criticism for its morbidity and mortality rates. This consequentially resulted in a lack of randomized trials being conducted and translates into a lack of the most reliable form of scientific evidence in clinical research, hence limiting its general acceptance. OBJECTIVE: : To report the morbidity and mortality outcomes of CRS and HIPEC from all institutions performing this treatment as a prelude toward establishing the safety of this treatment for peritoneal carcinomatosis. METHODS: : A systematic review of relevant studies before August 2008 was performed. Each study was appraised using a predetermined protocol. The quality of studies was assessed. The morbidity and mortality of the treatment were synthesized through a narrative review with full tabulation of results of all included studies. CONCLUSIONS: : The morbidity and mortality outcomes of CRS and HIPEC are similar to a major gastrointestinal surgery, such as a Whipple's procedure. To derive the maximal benefit of this treatment, careful patient selection with an optimal level of postoperative care must be advocated to avoid undesirable complications of this treatment. PMID- 19474693 TI - Mortality in medicare patients undergoing surgery in July in teaching hospitals. AB - OBJECTIVE: To determine whether operative mortality rates at teaching hospitals in the United States are higher in July, the start of the academic year. SUMMARY BACKGROUND DATA: Surgical patients at teaching hospitals often worry about the involvement of inexperienced physician trainees in their care. METHODS: This retrospective cohort study included all Medicare recipients undergoing 1 of 7 diverse inpatient procedures at teaching hospitals between 2003 through 2006 (N = 320,216). Teaching status was defined both by membership in the United States Council of Teaching Hospitals and by hospital ratio of trainees to beds. We compared operative mortality rates in July relative to all other months, adjusting for potentially confounding patient characteristics. The main outcome measure was operative mortality (before discharge or within 30 days of procedures). RESULTS: Adjusted operative mortality rates were no higher in July than in other months combined for all procedures, including coronary artery bypass grafting, carotid endarterectomy, repair of nonruptured abdominal aortic aneurysms, colectomy, pancreatectomy, esophagectomy, and repair of hip fracture. Trend analysis revealed no significant monthly or seasonal variation in operative mortality rates. CONCLUSIONS: Operative mortality rates do not decline as surgical trainees acquire more experience during the academic year. With respect to mortality, July is a safe month to have major surgery in teaching hospitals in the United States. PMID- 19474694 TI - Observational teamwork assessment for surgery: construct validation with expert versus novice raters. AB - OBJECTIVE: To test the construct validity of the Observational Teamwork Assessment for Surgery (OTAS) tool. SUMMARY BACKGROUND DATA: Poor teamwork in surgical teams has been implicated in adverse events to patients. The OTAS is a tool that assesses teamwork in real time for the entire surgical team. Existing empirical research on OTAS has yet to explore how expert versus novice tool users use the tool to assess teamwork in the operating room. METHODS: Data were collected in 12 elective procedures by an expert/expert (N = 6) and an expert/novice (N = 6) pair of raters. Five teamwork behaviors (communication, coordination, leadership, monitoring, and cooperation) were scored via observation pre, intra, and postoperatively by blind raters. RESULTS: Significant and sizeable correlations were obtained in 12 of 15 behaviors in the expert/expert pair, but only in 3 of 15 behaviors in the expert/novice pair. Significant differences in mean scores were obtained in 3 of 15 behaviors in the expert/expert pair, but in 11 of 15 behaviors in the expert/novice pair. Total OTAS scores exhibited strong correlations and no significant differences in ratings in the expert/expert pair. In the expert/novice pair no correlations were obtained and there were significant differences in mean scores. The overall size of inconsistency in the scoring was 2% for expert/expert versus 15% for expert/novice. CONCLUSIONS: OTAS exhibits adequate construct validity as assessed by consistency in the scoring by expert versus novices-ie, expert raters produce significantly more consistent scoring than novice raters. Further validation should assess the learning curve for novices in OTAS. Relationships between OTAS, measures of technical skill, and behavioral responses to surgical crises should also be quantified. PMID- 19474695 TI - Long-term survival after liver resection for colorectal liver metastases in patients with hepatic pedicle lymph nodes involvement in the era of new chemotherapy regimens. AB - SUMMARY AND BACKGROUND: Survival benefit, in patients with colorectal liver metastases (CLM) and hepatic pedicle lymph nodes (HPLN) involvement along the common hepatic artery and celiac axis (area 2 or distal) has not been observed. However, these results are based on historical series, using suboptimal chemotherapy drugs. OBJECTIVE: The aim of the present study is to investigate the impact of HPLN involvement on survival after resection for CLM in the era of the new chemotherapy regimens. PATIENTS AND METHODS: Between January 2000 and June 2006, 45 high risk consecutive patients presenting all with pathologically proven HPLN metastases were identified from a prospectively maintained database. Prognostic factors for survival and recurrence were analyzed. RESULTS: The mean follow-up was 25.5 months. HPLN involvement was located in area 1 in 17 patients, area 2 in 10, and both area 1 and 2 were involved in 18 patients. The overall 3- and 5-year survival rates were 29.7% and 17.3%, respectively. The median survival was 20.9 months. Three patients are alive and disease-free at 32.4, 33.5, and 46.9 months, respectively. The multivariate analysis showed that the carcinoembryonic antigen blood level before hepatectomy, a curative intent R0 liver resection, the ratio of involved/total resected HPLN, and an adjuvant chemotherapy after liver resection were independent risk factors for overall survival. CONCLUSIONS: This study showed that the localization of HPLN metastases within area 1 or 2 does not anymore affect survival after CLM resection. Furthermore, this study provides a support to perform a routine HPLN dissection in high risk patients undergoing liver resection for CLM to recognize HPLN involvement, to improve the ratio of involved/total resected lymph nodes, and to assign the patients for an adjuvant chemotherapy. Finally, these results indicate that curative intent R0 liver resection with HPLN dissection can offer the only potential cure for patients with CLM who present with HPLN involvement. PMID- 19474696 TI - TMPM-ICD9: a trauma mortality prediction model based on ICD-9-CM codes. AB - OBJECTIVE: To develop and validate a new ICD-9 injury model that uses regression modeling, as opposed to a simple ratio measurement, to estimate empiric injury severities for each of the injuries in the ICD-9-CM lexicon. BACKGROUND: The American College of Surgeons now requires International Classification of diseases ninth Edition (ICD-9-CM) codes for injury coding in the National Trauma Databank. International Classification of diseases ninth Edition Injury Severity Score (ICISS) is the best-known risk-adjustment model when injuries are recorded using ICD-9-CM coding, and would likely be used to risk-adjust outcome measures for hospital trauma report cards. ICISS, however, has been criticized for its poor calibration. METHODS: We developed and validated a new ICD-9 injury model using data on 749,374 patients admitted to 359 hospitals in the National Trauma Databank (version 7.0). Empiric measures of injury severity for each of the trauma ICD-9-CM codes were estimated using a regression-based approach, and then used as the basis for a new Trauma Mortality Prediction Model (TMPM-ICD9). ICISS and the Single-Worst Injury (SWI) model were also re-estimated. The performance of each of these models was compared using the area under the receiver operating characteristic (ROC), the Hosmer-Lemeshow statistic, and the Akaike information criterion statistic. RESULTS: TMPM-ICD9 exhibits significantly better discrimination (ROCTMPM = 0.880 [0.876-0.883]; ROCICISS = 0.850 [0.846-0.855]; ROCSWI = 0.862 [0.858-0.867]) and calibration (HLTMPM = 29.3 [12.1-44.1]; HLICISS = 231 [176-279]; HLSWI = 462 [380-548]) compared with both ICISS and the Single Worst Injury model. All models were improved with the addition of age, gender, and mechanism of injury, but TMPM-ICD9 continued to demonstrate superior model performance. CONCLUSIONS: Because TMPM-ICD9 uniformly out-performs ICISS and the SWI model, it should be used in preference to ICISS for risk-adjusting trauma outcomes when injuries are recorded using ICD9-CM codes. PMID- 19474697 TI - Complement-mediated ischemia-reperfusion injury: lessons learned from animal and clinical studies. AB - Ischemia-reperfusion (I/R) injury provides a substantial limitation to further improvements in the development of therapeutic strategies for ischemia-related diseases. Studies in animal I/R models, including intestinal, hindlimb, kidney, and myocardial I/R models, have established a key role of the complement system in mediation of I/R injury using complement inhibitors and knock-out animal models. As complement activation has been shown to be an early event in I/R injury, inhibiting its activation or its components may offer tissue protection after reperfusion. However, clinical study results using complement inhibitors have largely been disappointing. Therefore, identification of a more specific pathogenic target for therapeutic intervention seems to be warranted. For this purpose more detailed knowledge of the responsible pathway of complement activation in I/R injury is required. Recent evidence from in vitro and in vivo models suggests involvement of both the classic and the lectin pathways in I/R injury via exposition of neo-epitopes in ischemic membranes. However, most of these findings have been obtained in knock-out murine models and have for a large part remained unconfirmed in the human setting. The observation that the relative role of each pathway seems to differ among organs complicates matters further. Whether a defective complement system protects from I/R injury in humans remains largely unknown. Most importantly, involvement of mannose-binding lectin as the main initiator of the lectin pathway has not been demonstrated at tissue level in human I/R injury to date. Thus, conclusions drawn from animal I/R studies should be extrapolated to the human setting with caution. PMID- 19474698 TI - Metastasis to the sigmoid or sigmoid mesenteric lymph nodes from rectal cancer. AB - OBJECTIVE: We analyzed metastases to the sigmoid and sigmoid mesenteric lymph nodes from rectal cancer. BACKGROUND: It has been reported that rectal cancer spreads upward and lateral. However, metastasis to the sigmoid mesenteric or sigmoid nodes from rectal cancer has been rarely reported. METHODS: We enrolled 347 patients who underwent curative resection for rectal cancer with proven lymph node metastases and dissection of the sigmoid and sigmoid mesenteric lymph nodes. Lymph node classification was performed by the colorectal surgeon and the lymph nodes were sent to pathology. Two hundred ninety sigmoid mesenteric and 248 sigmoid lymph node dissections were confirmed by pathologic examination. RESULTS: There were 185 and 162 patients with extraperitoneal and intraperitoneal rectal cancers, respectively. The T categories were T1 in 4 patients (1.2%), T2 in 25 patients (7.2%), T3 in 252 patients (72.6%), and T4 in 66 patients (18.8%). The N categories were N1 in 216 patients (62.2%) and N2 in 131 patients (37.8%). Metastases to the sigmoid and sigmoid mesenteric lymph nodes occurred in 60 (20.7%) and 28 patients (11.3%), respectively. Metastases to the sigmoid or sigmoid mesenteric lymph nodes, without metastases to the superior rectal and inferior mesenteric lymph nodes, developed in 18 patients (5.2%). Compared with patients without sigmoid mesenteric lymph node metastases, N2 category disease, and poor differentiation, overall recurrence was more common in patients with sigmoid mesenteric lymph node metastases. Patients with sigmoid lymph node metastases were common in the N2 category of disease. However, the number of retrieved lymph nodes, and the overall and local recurrence rates were not significantly different. Seventeen of 18 patients with only sigmoid mesenteric or sigmoid lymph node metastases had N1 category disease; 8 and 10 patients had extraperitoenal and intraperitoneal rectal cancers, respectively. For patients with N1 category disease, there was no difference in the overall and local disease recurrence rates among the patients. CONCLUSION: Sigmoid mesenteric or sigmoid lymph node metastases developed in 23.2% of patients in the present study. But, there were no differences in the cancer-specific survival, overall and local disease recurrence rates in the patients with sigmoid mesenteric or sigmoid lymph node metastases. PMID- 19474699 TI - Risk factors for clinical manifestations in carriers of Factor V Leiden and prothrombin gene mutations. AB - Carriers of Factor V Leiden and prothrombin G20210A gene mutations have an increased risk of developing thromboembolic events and adverse outcomes of pregnancy. The objective of the present study was to identify risk factors which may predispose carriers of Factor V Leiden and/or prothrombin G20210A gene mutations to develop thromboembolic events and adverse outcomes of pregnancy. A retrospective case-control study of 217 carriers of Factor V Leiden and/or prothrombin G20210A gene mutations at two tertiary centers between January 2000 and December 2006. Symptomatic carriers (cases) were compared with asymptomatic carriers (controls) for the following risk factors: environmental, cardiovascular, family history of thrombosis, and presence of other thrombophilias. For female carriers, we included the use of female hormones, pregnancy, and the postpartum period. Of the 217 carriers, there were 155 (71%) cases and 62 (29%) controls. Of the 155 cases, 90 (58%) had venous thrombosis and 26 (17%) arterial thrombosis. Among the 123 symptomatic female carriers, 55 (45%) had recurrent pregnancy losses and nine (7%) other adverse outcomes of pregnancy. The postoperative state and the presence of antiphospholipid antibodies were risk factors for thromboembolic events and adverse outcomes of pregnancy in 10 (6%) and 22 (13%) cases, respectively. The presence of antiphospholipid antibodies in symptomatic carriers increased the risk of developing thromboembolic events 4.4 fold. The postoperative state and the presence of antiphospholipid antibodies were significant risk factors for thromboembolic events and adverse outcomes of pregnancy among Factor V Leiden and/or prothrombin G20210A gene mutation carriers. Testing for the presence of antiphospholipid antibodies may be warranted in Factor V Leiden and/or prothrombin G20210A gene mutation carriers who develop these adverse clinical manifestations. PMID- 19474700 TI - Immune thrombocytopenia associated with Mycoplasma pneumoniae infection: a case report and review of literature. AB - Although extra-pulmonary manifestations of Mycoplasma pneumoniae are well described, immune thrombocytopenia associated with M. pneumoniae is rarely reported. We describe a woman who developed immune thrombocytopenic purpura during an acute mycoplasma infection. The clinical features and outcomes of all previously reported cases are reviewed, and possible mechanisms underlying this association are discussed. Immune thrombocytopenic purpura should be considered early in patients with thrombocytopenia and mycoplasma infections, with the institution of usual therapy for immune thrombocytopenic purpura. PMID- 19474701 TI - Kinetics of D-dimer after general surgery. AB - D-dimers may be elevated after surgery. However, the kinetics of postoperative D dimers remains unknown hampering the use of D-dimer testing in surgical patients with suspected venous thromboembolism. D-dimer levels were prospectively measured in 154 patients after general surgery at predefined time points (kinetics were determined in an initial cohort of 108 patients; for validation, these findings were applied to a second cohort of 46 patients). Clinical factors influencing the peak of D-dimers were analyzed using multivariate regression. Surgical operations were stratified based on severity (type I: not entering abdominal cavity; type II: intraabdominal; type III: retroperitoneal/liver surgery). D-dimer levels increased postoperatively reaching a peak on day 7. After type I surgery, peak D dimer levels did not exceed normal range (300 ng/ml, 100-500). After type II procedures, peak D-dimer level was 1500 ng/ml (200-7800) and returned to normal values after 25 days (+/-14). Peak level was 4000 ng/ml (500-14 400) after type III surgery normalizing within 38 days (+/-11). Clearance of D-dimer was exponential after having reached the peak with 6.0% per day (95% confidence interval 4.8-7.1%). By this clearance, D-dimer values could be adequately predicted in the validation cohort after day 7 (r2 = 0.63). Peak D-dimer levels were independently influenced by the type of surgery (P < 0.001), the operation time (P < 0.001) and by preoperatively elevated D-dimer levels (P < 0.001). Based on this data, duration of postoperative D-dimer elevation after abdominal surgery is predictable. This study indicates for the first time when D-dimers may be used again in the diagnostic algorithm for venous thromboembolism exclusion after surgery in patients with low or moderate clinical probability. PMID- 19474702 TI - Kallikrein-kinin system and fibrinolysis in hereditary angioedema due to factor XII gene mutation Thr309Lys. AB - In a subgroup of hereditary angioedema (HAE) patients with normal C1-esterase inhibitor levels, HAE is caused by a Thr309Lys mutation in the coagulation factor XII (F12) gene. The aim of this study was to examine elements of the kallikrein kinin system ('contact system') and the downstream-linked coagulation, complement and fibrinolytic systems in the plasma of six patients with HAE caused by the Thr309Lys mutation and healthy probands. Blood samples were taken from participants during the symptom-free interval between attacks. Samples were analyzed for activity and concentrations of components of the kallikrein-kinin system and linked enzyme systems. The mean FXII clotting activity was 90% in patients with the FXII mutation, and the concentration of FXIIa was 4.1 ng/ml; this did not differ from healthy probands. Mean prekallikrein amidolytic activity and high-molecular-weight kininogen clotting activity were 130 and 144%, respectively, both higher than in healthy probands. The mean kallikrein-like activity of the HAE patients was 11.4 U/l and did not differ from healthy probands. There was no difference in FXII surface activation by silicon dioxide or in kallikrein-like activity with and without activation by dextran sulfate. Contrary to the results of a recently published study, no indication that the Thr309Lys mutation causes a 'gain-of-function' of FXIIa was observed in this investigation. PMID- 19474703 TI - Caudal duplication syndrome with unilateral hypoplasia of the pelvis and lower limb and ventriculoseptal heart defect in a mother and features of VATER association in her child. AB - We report the case of a 22-year-old female with caudal duplication syndrome, who in addition to intestinal duplication, imperforate anus, a dydelphic uterus and a single kidney also had a ventricular septal defect and hypoplasia of the left pelvis, leg, labia majora and left side of a duplicated vagina. She gave birth to a male baby with features of the VATER association including a tracheooesophageal fistula, a ventriculoseptal defect, an atrial septal defect and mild hypospadias. We suggest that caudal duplication syndrome and the VATER association may overlap and our two cases suggest possible autosomal dominant inheritance. PMID- 19474704 TI - The phenotypic spectrum of trisomy 2: report of two new cases. AB - We describe two cases of trisomy 2. The first case is a child with mosaic trisomy 2 who presented with mental retardation, multiple congenital anomalies, and dysmorphic findings similar to Pallister-Killian syndrome. The second case was an acardiac and acranial fetus with complete trisomy 2. We review the phenotypic spectrum associated with trisomy 2. PMID- 19474705 TI - Two siblings with microcephaly, growth retardation, cataract, hearing loss, and unusual appearance. PMID- 19474706 TI - Food protein-induced enterocolitis syndrome. AB - PURPOSE OF REVIEW: To review current knowledge and recent advances in food protein-induced enterocolitis syndrome (FPIES). RECENT FINDINGS: Rice is the most common solid food causing FPIES. Rice FPIES is associated with more severe reactions than other foods. Infants presenting acutely may be hypothermic (<36 degrees C) and have thrombocytosis. Finding of hypoalbuminemia and weight gain less than 10 g/day helps to differentiate chronic infantile cow's milk FPIES from infectious causes. Gastric juice leukocytes more than 10 cells per high-power field are found in infants with positive oral food challenge to cow's milk. SUMMARY: FPIES is a non-IgE-mediated gastrointestinal food hypersensitivity disorder. Food protein-activated intestinal lymphocytes elaborate inflammatory cytokines that result in increased intestinal permeability, malabsorption, dysmotility, emesis, diarrhea, pain, and failure to thrive. Decreased intestinal transforming growth factor beta and increased TNFalpha may be important in FPIES. Cow's milk and soy are the most common causes of FPIES, but cereal grains (rice, oat, and barley), fish, poultry, and vegetables may also cause FPIES. The majority of FPIES resolve by age of 3 years. PMID- 19474707 TI - Role of T cells in nonimmediate allergic drug reactions. AB - PURPOSE OF REVIEW: This review presents the current knowledge of the role of T cells in drug allergy manifesting as exanthematous, pustular and bullous skin diseases, collectively referred to as nonimmediate allergic drug reactions. RECENT FINDINGS: Both CD4+ and CD8+ T cells producing type 1 and type 2 cytokines and endowed with cytotoxic properties are involved in nonimmediate allergic drug reactions. Recent studies have confirmed that CD8+ T cells play a major role in the pathophysiology of nonimmediate allergic drug reactions, and have characterized new cytotoxic molecular pathways responsible for the severity of the bullous forms of nonimmediate allergic drug reactions. SUMMARY: Nonimmediate allergic drug reactions are mediated by T cells and mostly affect the skin. Nonimmediate allergic drug reactions comprise several diseases ranging from the frequent and benign maculo-papular exanthema to the severe and rare toxic epidermal necrolysis. Progress in the knowledge of the pathophysiology of nonimmediate allergic drug reactions comes from a better understanding of the mechanisms of drug recognition by T cells and from a careful analysis of the phenotype and functions of CD4+ and CD8+ T cells infiltrating the skin lesions. Recent studies have confirmed that the different clinical forms of nonimmediate allergic drug reactions are associated with distinct types of T cell-mediated skin inflammation. However, CD8+ T cells appear as major effector T cells in most of the nonimmediate allergic drug reactions. Future studies to analyze the early cellular and molecular events leading to the development of the allergic skin reaction will be helpful in order to define diagnostic and therapeutic targets. PMID- 19474708 TI - Stinging Hymenoptera and mastocytosis. AB - PURPOSE OF REVIEW: Patients suffering from mastocytosis are at risk for a particularly severe Hymenoptera sting anaphylaxis. The purpose of this review is to evaluate the current knowledge on pathophysiologic events, which might explain the specific risk of patients with mastocytosis. RECENT FINDINGS: Mast cell products can neutralize major toxins of snake or bee venoms. beta-tryptase from mast cells is able to degrade allergens and IgE antibodies. Thus, mast cells and their mediators should protect patients from venom toxicity and should also lead to a decreased allergenicity. However, these theoretically beneficial effects of mast cells on downregulating allergic immediate type reactions are insufficient to protect patients with mastocytosis from severe anaphylaxis. In contrast, these patients are at an even higher risk. Many compounds of Hymenoptera venom can induce Fcepsilon receptor-independent mast cell degranulation. In the context of mast cell activation induced by Hymenoptera venom, FcepsilonRI-dependent stimulation of mast cells via bridging of specific IgE-antibodies may be of particular importance. Abundance and dysfunction of mast cells in patients with mastocytosis may explain a significant portion of the particularly high anaphylactic risk in patients with mastocytosis. SUMMARY: The particular anaphylactic risk of patients with mastocytosis results from a variety of mechanisms. However, their individual contribution still needs further clarification. PMID- 19474709 TI - Fixed drug eruption: pathogenesis and diagnostic tests. AB - PURPOSE OF REVIEW: Fixed drug eruption is a simplified disease model for elucidating the mechanism(s) of how skin inflammation is induced by skin-resident T cells. In this review, we focus on how the presence of intraepidermal CD8+T cells resident in the fixed drug eruption lesions can provide exciting new clues to our understanding of pathomechanisms of inflammatory skin diseases. RECENT FINDINGS: Intraepidermal CD8+T cells with an effector-memory phenotype resident in fixed drug eruption lesions have a major contributing role in the development of localized tissue damage. Activation of these CD8+T cells is sufficient for triggering the lesion, however, but not sufficient to cause extensive tissue damage observed in the fully evolved lesions; additional recruitment of CD4+ and CD8+T cells to a specific tissue site would also contribute to the late stage of lesion development. The influx of regulatory T cells into the epidermis observed in fully evolved lesions would serve to limit harmful immune reactions. Consistent with this, positive patch test reactions are only observed at the site of previous lesions harboring significant numbers of intraepidermal CD8+T cells. SUMMARY: Intraepidermal CD8+T cells may represent double-edged swords of the skin immune system with protective and destructive capacity. PMID- 19474710 TI - Strategies to minimize bleeding complications of percutaneous coronary intervention. AB - PURPOSE OF REVIEW: Bleeding has recently been identified as a major adverse outcome in patients with acute coronary syndromes. In this review, the importance of the association of bleeding with mortality and strategies to reduce bleeding with percutaneous coronary intervention are discussed. RECENT FINDINGS: Nine trials have shown an association of bleeding with mortality. The influence of major bleeding is at least equivalent to the effect of a myocardial infarction. In order to reduce bleeding, individualized risk assessment should be performed and attention paid to choice of access, antithrombotic, dose of antithrombotic, avoidance of crossing over from one antithrombotic to another, smaller sheaths and early removal as well as choice of P2Y12 inhibitor. SUMMARY: Individualizing treatment and strategies to reduce both ischemic events and bleeding will improve patient outcomes. PMID- 19474711 TI - The use of real-time three-dimensional echocardiography for the quantification of left ventricular volumes and function. AB - PURPOSE OF REVIEW: The purpose of this review is to provide readers with an update on the latest developments and the current status of the real-time three dimensional echocardiographic (RT3DE) quantitative evaluation of left ventricular volumes and function. RECENT FINDINGS: In recent years, the growing availability of RT3DE imaging technology, its ease of use and its multiple attractive features have sparked significant interest in the echocardiography community, resulting in a large number of research papers, most of which have endorsed RT3DE imaging for clinical use by demonstrating its unique capabilities in different scenarios. In parallel, the clinical acceptance of this new tool has broadened significantly. SUMMARY: Although the clinical value of RT3DE evaluation of the left ventricle is already well established, future improvements will determine whether this methodology can become the new standard reference technique for accurate and repeatable measurement of left ventricular volumes, mass, regional left ventricular function and dyssynchrony. PMID- 19474712 TI - Malnutrition and wasting in renal disease. AB - PURPOSE OF REVIEW: Malnutrition and accelerated catabolism frequently complicate chronic kidney disease and end-stage renal disease. This review provides an update on the recent advances in the understanding of the mechanisms underlying protein-energy wasting, both in experimental and human models, and on the currently available therapeutic approaches. RECENT FINDINGS: Increased levels of circulating cytokines, metabolic acidosis, oxidative stress and insulin resistance all appear to be variably implicated in muscle protein breakdown during end-stage renal disease and dialysis. The individual role of each component in the pathogenesis of chronic kidney disease-related wasting is still unclear, but recent clinical data show a positive relationship between inflammation and muscle protein catabolism as a major contributing factor. SUMMARY: The basis for appropriate therapeutic approaches to protein-energy wasting in chronic kidney disease and end-stage renal disease relies entirely on the understanding of its pathophysiology. Our knowledge of the pathogenesis of malnutrition and hypercatabolism in renal disease is still limited and mostly based on experimental data, but the currently available evidence suggests that multimodal preventive and therapeutic strategies should be entertained. PMID- 19474713 TI - Healthy obesity. AB - PURPOSE OF REVIEW: To introduce the healthy obese phenotype, characterized by favorable cardiometabolic risk factors despite excess adipose tissue. The epidemiology of the healthy obese phenotype is presented, including associated risk of cardiovascular disease (CVD), and potential biologic mechanisms which may give rise to the phenotype are discussed. RECENT FINDINGS: Although it appears that approximately 30% of obese individuals maintain healthy cardiometabolic profiles, little published data exist examining the healthy obese phenotype. The healthy obese do not appear to be at increased risk of incident CVD events compared with at-risk obese, and the location of adipose tissue and the metabolic characteristics of the fat in a given location, including the presence of ectopic fat and associated adipocytokine response, may give rise to the phenotype. Recent data also suggest that weight loss among healthy obese may adversely impact their favorable cardiometabolic profile. SUMMARY: A high prevalence of the healthy obese phenotype has been reported, and these individuals appear to be at no increased risk of CVD. Further research is needed into the mechanisms that allow these individuals to maintain low risk of CVD despite excess adiposity and appropriate weight loss recommendations for this group. PMID- 19474714 TI - Catabolism of lipoproteins and metabolic syndrome. AB - PURPOSE OF REVIEW: Metabolic syndrome is very common and is associated with significantly increased risk for both cardiovascular disease and type 2 diabetes. At present, no unifying mechanism can explain it. However, insulin resistance is a key feature of this syndrome, plays a key role in triglyceride metabolism and contributes to dyslipidemia and development of type 2 diabetes. Here, we review the mechanisms involved in the overproduction of large VLDL and their catabolism and finally potential therapeutic targets to provide a more complete approach to treatment of these lipid abnormalities. RECENT FINDINGS: Dyslipidemia plays an important role in the development of atherosclerosis and is mainly associated by the hepatic overproduction of large triglyceride-rich VLDL, low levels of HDL cholesterol and high levels of small, dense, LDL cholesterol particles. It is thus of special interest to understand the mechanism involved in the hepatic synthesis of lipoproteins and the degradation of these lipoproteins that depend, to a large extent, on insulin action. SUMMARY: The atherogenic lipid abnormalities observed in the metabolic syndrome may require a combination of drugs such as statins and HDL-raising agents to provide a more complete approach to treating dyslipidemia and reducing cardiovascular risk. PMID- 19474715 TI - Advancing from immunonutrition to a pharmaconutrition: a gigantic challenge. AB - PURPOSE OF REVIEW: This review presents some difficulties encountered to develop and translate immunonutrition into clinical practice, and suggests moving forward to a pharmaconutrition approach. RECENT FINDINGS: Immunonutrition suffers from inconclusive and contradictory data due to the design of many of experiments and clinical studies conducted so far. The concept of a single immunonutrient formula applicable to various types of patients has also contributed to leave the medical world in a state of uncertainty. We propose to move forward to the concept of pharmaconutrition where a disease-dedicated nutrition therapy is developed following a rigorous step-by-step procedure. Nutrients are selected according to their pharmacological properties and after an in-depth evaluation of their biological interactions when mixed together. The optimum administration schedule (i.e. dose, route, timing and duration) of the new formulae is then determined in well conducted projective clinical trials where it is administered apart from the standard nutrition to ensure full delivery of the expected doses. SUMMARY: This review suggests moving forward to a pharmaconutrition approach where a rigorous step-by-step procedure would allow overcoming of the difficulties encountered to translate immunonutrition into clinical practice. PMID- 19474716 TI - Role of dietary mutagens in cancer and atherosclerosis. AB - PURPOSE OF REVIEW: To provide an updated summary of dietary mutagens and their potential role in the etiology of cancer and atherosclerosis. RECENT FINDINGS: Compelling evidence supports an accumulation of somatic mutations during carcinogenesis, leading to the activation of oncogenes or inactivation of tumor suppressor genes or both. There is also suggestive evidence that mutation provides an early event in atherosclerosis. Genome-wide association studies (GWAS) identify genes associated with familial cancers and atherosclerosis, but genes involved in sporadic events are less well characterized. Many dietary components are mutagenic, including natural dietary components, mutagens generated during cooking and processing of food or through contamination. Molecular epidemiology associates specific mutagens with specific types of cancer. Although chromosome mutations may provide a risk biomarker for atherosclerosis, they are not necessarily causal. SUMMARY: Association studies, supported by molecular epidemiology, provide evidence that certain dietary mutagens, including aflatoxin B1, aristolochic acid and benzo[a]pyrene, are causal in some human cancers. Similar studies have correlated the level of oxidative DNA damage, DNA adducts and clastogenesis in arterial smooth muscle cells with atherogenic risk factors described through traditional epidemiology. However, establishing whether or not dietary mutagens lead to mutations that are causal in atherosclerosis remains a challenge for the newer genomic technologies. PMID- 19474717 TI - Short bowel syndrome: the role of GLP-2 on improving outcome. AB - PURPOSE OF REVIEW: The medical management of short bowel syndrome frequently requires lifelong parenteral nutrition. Methods of increasing intestinal absorption and reducing parenteral nutrition dependence, by improving postresection intestinal adaptation, are increasingly being explored. Glucagon like peptide-2 (GLP-2) is an important intestinotrophic growth factor and mediator of intestinal adaptation. This review summarizes our current understanding of GLP-2 physiology and provides an update on clinical trials in short bowel syndrome and related conditions. RECENT FINDINGS: There is growing understanding how the effects of GLP-2 are mediated by downstream effectors such as insulin-like growth factor-1. In the treatment of short bowel syndrome, GLP-2 and the long-acting GLP-2 analogue teduglutide (Gattex) are effective in improving fluid absorption. A recent multicentre, placebo-controlled study demonstrates that this can translate into meaningful reductions in parenteral nutrition requirements. Treatment dose and timing of treatment initiation might influence the mucosal growth response. Most of the small intestine has to be preserved to facilitate the previously documented benefits of GLP-2 on bone metabolism. Therapeutic uses of GLP-2 in other gastrointestinal conditions are being explored. GLP-2 treatment appears well tolerated, although concerns about the long-term use of this growth-promoting agent remain. SUMMARY: GLP-2 therapy holds promise as an adjuvant treatment modality for short bowel syndrome and other gastrointestinal disorders. PMID- 19474718 TI - Nutrition in heart failure: an update. AB - PURPOSE OF REVIEW: Chronic heart failure (CHF) is increasingly recognized as a multisystem disease with important comorbidities such as anemia, insulin resistance, autonomic dysbalance, or cardiac cachexia. RECENT FINDINGS: Apart from these perturbations, increasing evidence points to alterations in intestinal morphology, permeability, and absorption function in patients with CHF. This review provides an overview of the sonographic, histological, and functional abnormalities of different gastrointestinal regions. This intestinal dysfunction and disturbed intestinal barrier may lead to both the chronic inflammatory state and catabolic/anabolic imbalance as seen in cardiac cachexia, as a terminal stage of CHF, which carries a particularly poor prognosis. This review highlights the current knowledge of nutritional abnormalities that may occur in CHF, including fat, carbohydrates, proteins, water, and micronutrients. The regulation of feeding is discussed, as are nutritional strategies with potentially anti inflammatory effects in the treatment of CHF. SUMMARY: The gut and its role for inflammation and dietary interventions in heart failure patients are a crucial target of further heart failure research. PMID- 19474719 TI - Metabolic benefits from Sirt1 and Sirt1 activators. AB - PURPOSE OF REVIEW: To evaluate the role of mammalian Sirt1 and Sirt1 activators in the protection from metabolic disorders such as diet-induced obesity, diabetes type 2, or nonalcoholic fatty liver disease. RECENT FINDINGS: Sirtuins are highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that are activated by NAD+ and inhibited by NAD in its reduced form (NADH). Sirtuins act as cellular energy sensors that deacetylate numerous proteins involved in energy and glucose homeostasis, which in turn induce a wide range of physiological changes that counteract detrimental effects of metabolic stressors. SUMMARY: Sirt1 targets numerous proteins, including peroxisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma coactivator (PGC)-1alpha, uncoupling protein 2 (UCP2), and nuclear factor-kappa B, which play key roles in various metabolic disorders. This review summarizes these key targets of Sirt1 and the physiological relevance of those interactions. Also, new results on Sirt1 knockout and overexpressor mouse models are presented to substantiate metabolic benefits from Sirt1 activation. Finally, this review gives an overview on recent efforts to activate Sirt1 pharmacologically by using resveratrol or small molecule Sirt1 activators with improved biopotency. PMID- 19474720 TI - Metabolomics in evaluation of glucose disorders. AB - PURPOSE OF REVIEW: Recent advances in metabolomic tools now permit to characterize dysregulated metabolic pathways in various diseases associated with the identification of sensitive and specific early responding biomarkers that are critical both for the diagnosis of the type of insult as well as for the selection and evaluation of therapy. RECENT FINDINGS: This short review describes progresses made in analytical science and their applications in the field of glucose disorders. Recent studies focused mainly on type 2 diabetes both in human and animal models in order to validate early biomarkers and effects of drugs on disease progression. The potential of using the metabolomic approach was also demonstrated for diagnosing diabetic complications such as diabetic nephropathy. SUMMARY: In addition to its application in the discovery of disease biomarkers, metabolomics can contribute to the elucidation of pathophysiological mechanisms. PMID- 19474722 TI - The metabolic syndrome: how it may influence hepatic stellate cell activation and hepatic fibrosis. AB - PURPOSE OF REVIEW: To highlight the metabolic or inflammatory components, deregulated in or pathogenic for the metabolic syndrome, that may, directly or indirectly, modulate hepatic fibrogenesis. RECENT FINDINGS: Advanced glycation end products signal profibrogenetic transformation of hepatic stellate cells. Altered adipocytokines favor insulin resistance and steatosis. They participate to the proinflammatory status of the metabolic syndrome. Among them, leptin has been shown to directly enhance fibrogenesis, whereas adiponectin has shown antifibrotic properties. The renin-angiotensin system, a component of arterial hypertension, is activated in the diseased liver, and there is convincing evidence that blockade of angiotensin II signaling attenuates fibrosis. Endocannabinoids, whose hepatic production and signaling capability are increased with insulin resistance and obesity, signal profibrotic response via the preponderant receptor, cannabinoid receptor 1, whereas antifibrotic and anti inflammatory signals are rather generated via stimulation of cannabinoid receptor 2. Finally, recent data demonstrate that modulation of innate immunity, particularly modulation of natural killer and natural killer T cells, has potential roles in the resolution of steatohepatitis and fibrosis. SUMMARY: Several features associated with the metabolic syndrome can undoubtedly modulate liver fibrosis. More studies are needed to identify those that are prominent determinants of fibrosis in the metabolic syndrome and the benefit of their targeting for fibrosis prevention and treatment. PMID- 19474723 TI - Intestinal gluconeogenesis: key signal of central control of energy and glucose homeostasis. AB - PURPOSE OF REVIEW: It has been established that the gut is much more than a digestive tract. It has the capacity to participate in the control of energy homeostasis via the secretion of various hormones. It can also contribute to the control of glucose homeostasis via its high glycolytic capacity and a recently described function, gluconeogenesis. RECENT FINDINGS: In addition to its quantitative role in endogenous glucose production, qualitative roles (i.e. central signaling) were recently described for intestinal gluconeogenesis. In relation to the control of energy homeostasis, intestinal gluconeogenesis, via its detection by a hepatoportal glucose sensor, is able to generate a central signal of control of food intake, resulting in enhanced satiety. This mechanism has been suggested to account for the well known satiety effect initiated by food protein. In relation to the control of glucose homeostasis, intestinal gluconeogenesis has been suggested to be a key factor of the central enhancement of insulin sensitivity for the whole body. It may especially account for the rapid amelioration of the parameters of insulin resistance occurring after gastric bypass, a specific type of surgery of obesity. SUMMARY: These new findings on the role of intestinal gluconeogenesis in the central control of energy and glucose homeostasis should be of interest for nutritionists and diabetologists. They pave the way to envision new strategies of prevention or treatment of obesity and type 2 diabetes in humans. PMID- 19474721 TI - SIRT1 and caloric restriction: an insight into possible trade-offs between robustness and frailty. AB - PURPOSE OF REVIEW: This review aims to summarize the importance of the mammalian nicotinamide adenine dinucleotide (NAD)-dependent deacetylase SIRT1 as a critical mediator that coordinates metabolic responses to caloric restriction and the recent progress in the development of SIRT1-targeted caloric restriction mimetics. It also discusses possible trade-offs between robustness and frailty in caloric restriction and the applicability of caloric restriction or SIRT1 targeted caloric restriction mimetics to humans. RECENT FINDINGS: Loss-of function and gain-of-function mouse studies have provided genetic evidence that SIRT1 is a key mediator that orchestrates the physiological response to caloric restriction. SIRT1-activating compounds function as potential caloric restriction mimetics, at least in part, through the activation of SIRT1 in vivo. SUMMARY: Increasing SIRT1 dosage/activity is effective to provide significant protection from high-fat diet-induced metabolic complications, suggesting that SIRT1 activation likely promotes robustness in the regulation of metabolism. However, caloric restriction itself and caloric restriction mimicry through systemic SIRT1 activation might also generate frailty in response to unexpected environmental stimuli, such as bacterial and viral infections. It will be of great importance to understand the principles of systemic robustness and its spatial and temporal dynamics for the regulation of aging and longevity in mammals in order to achieve an optimal balance between robustness and frailty in our complex physiological system. PMID- 19474724 TI - Endoscopic therapy of Barrett's esophagus. AB - PURPOSE OF REVIEW: Endoscopic therapy for early neoplasia arising in Barrett's esophagus has gained wide acceptance in the USA and Europe, and long-term results of endoscopic resection and photodynamic therapy and new ablation techniques are available now. This review summarizes the different indications for endoscopic treatment and the recent data on the different endoscopic treatment techniques. RECENT FINDINGS: Endoscopic treatment of high-grade intraepithelial neoplasia has proven to be well tolerated and effective even after a long-term follow-up of more than 5 years. Radiofrequency treatment seems to be an effective technique for ablation of Barrett's esophagus with low and high-grade intraepithelial neoplasia on short-term follow-up with a very low complication rate. Recent data were able to demonstrate that biomarkers can predict the treatment effect of photodynamic therapy and several risk factors for stricture formation after treatment could be identified. SUMMARY: Endoscopic therapy of early Barrett's neoplasia has proven to be well tolerated and effective and can be considered as the treatment of choice for most patients with this disease. Visible lesions should be treated by endoscopic resection in order to obtain a specimen for histological work up. The remaining nondysplastic Barrett's epithelium after complete resection of all neoplastic lesions should be ablated, for example, by radiofrequency treatment, to prevent metachronous or recurrent neoplasia. PMID- 19474725 TI - Advanced imaging of the gastrointestinal tract: research vs. clinical tools? AB - PURPOSE OF REVIEW: Diagnostic endoscopy has moved forward considerably in the recent years. Still, three major needs have to be satisfied: endoscopy should be able to detect a lesion, characterize the lesion, and then its nature should be confirmed. These steps should ideally translate into an immediate therapeutic decision. RECENT FINDINGS: High definition endoscopy has optimized our endoscopic view onto the mucosa and can be combined with digital surface enhancement modalities. Chromoendoscopy still holds a place to detect especially flat lesions in high-risk patients such as ulcerative colitis. Digital chromoendoscopy techniques such as narrow band imaging, i-scan, or Fuji intelligent chromo endoscopy offer new possibilities of easily and reversibly obtaining enhanced tissue contrast. Autofluorescence imaging uses tissue function to yield a pseudocolored image, and has potential to serve as a red flag technique for the detection of neoplastic lesions. Confocal laser endomicroscopy has for the first time provided real time microscopy. In addition to visualizing morphology, functional and molecular imaging open new horizons for the gastroenterologist. SUMMARY: Advanced imaging techniques have provided the endoscopist with an armamentarium of novel modalities for detection, characterization and microscopy of lesions during endoscopy. In addition, functional and molecular imaging give insight into dynamic processes of tissues in their natural surroundings. PMID- 19474726 TI - Natural orifice translumenal endoscopic surgery 2009: what is the future for the gastroenterologist? AB - PURPOSE OF REVIEW: In order to predict whether the gastroenterologist will have a role in the rapidly developing field of natural orifice translumenal endoscopic surgery (NOTES), it is helpful to examine the new developments in this field. Our goal in this review is to examine the recent developments in the field and study the gastroenterologists' role to best make this prediction. RECENT FINDINGS: Perhaps the most significant development in the field of NOTES has been the favorable patient and physician preferences for NOTES. There is evidence that patients would prefer NOTES cholecystectomy to laparoscopic cholecystectomy. The most common reason for this choice appears to be the lack of pain and visible scar. Another very significant development has been the reality of human NOTES procedures. Multiple centers have reported human NOTES procedures, including transgastric appendectomies, transgastric liver biopsies, transgastric tubal ligation and transvaginal cholecystectomy without major complications. Gastroenterologists' expertise with flexible endoscope was critical in the above cases. Recently, a few publications have also shown how gastroenterologists with expertise in endosonography can have a role in affirming safe access. SUMMARY: Although no one can predict with certainty where the field of NOTES will be in 1 year, it seems likely that gastroenterologist involvement will be necessary and advancements in this field will be applicable and diffuse into our daily practice. PMID- 19474727 TI - Use of surveillance data for prevention of healthcare-associated infection: risk adjustment and reporting dilemmas. AB - PURPOSE OF REVIEW: Healthcare-associated or nosocomial infection (HCAI) is of increasing importance to healthcare providers and the public. Surveillance is crucial but must be adjusted for risk, especially when used for interhospital comparisons or for public reporting. RECENT FINDINGS: Surveillance data are increasingly adjusted for risk factors for HCAI if meaningful comparisons are made between institutions or across national boundaries. Postdischarge surveillance is important in detecting those infections that may not present to the institution in which the original procedure occurred. Caution is urged when comparing data from two sources, for example, an active surveillance program and administrative datasets. The public reporting of HCAI rates can assist in improving the quality of healthcare, but to date there is little evidence that this is happening. In the United States, a number of states have introduced mandatory reporting of HCAIs, but there is considerable variation in what data are released, how these are reported and the rigor of the validation of the dataset. SUMMARY: The consumerization of healthcare requires a response from healthcare providers to engage with the public on how, when and what risk adjusted surveillance data to release. Information campaigns are required to ensure the public understand any publicly released data and its limitations. PMID- 19474729 TI - Targets for LDL-lowering therapy. AB - PURPOSE OF REVIEW: To compare non-HDL-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as targets for LDL-lowering therapy. The conventional approach is restricted to a comparison of in-trial data. Although essential, this overlooks the issue as to which marker better identifies residual risk after any particular treatment regimen. RECENT FINDINGS: Data from a series of recent studies, including Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin, Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy II, Treating to New Targets-Incremental Decrease in End Points Through Aggressive Lipid Lowering and Collaborative Atorvastatin Diabetes Study, demonstrating that apoB better identifies residual risk than non-HDL-C will be reviewed. SUMMARY: Comparing markers such as non-HDL C and apoB for the accuracy with which they identify risk during a trial is essential but not sufficient. It is also necessary to compare markers for how well they identify residual risk, and, in this regard, apoB clearly outperforms non-HDL-C. PMID- 19474728 TI - The roles of PON1 and PON2 in cardiovascular disease and innate immunity. AB - PURPOSE OF REVIEW: The paraoxonase (PON) gene family includes three members, PON1, PON2, and PON3. In-vitro and mouse studies have demonstrated that all three PONs are atheroprotective. Some, but not all, human epidemiologic studies have observed associations between PON gene polymorphisms and risk of cardiovascular disease (CVD). In this review, we summarize studies published within the last year, elucidating involvement of PON1 and PON2 in oxidative stress, CVD, and innate immune responses. RECENT FINDINGS: In a prospective study, the PON1 192QQ genotype and low PON1 activity were associated with increased systemic oxidative stress and increased risk for CVD. PON1 expression protected against Pseudomonas aeruginosa lethality in Drosophila, suggesting that PON1 can interfere with quorum sensing in vivo. PON2 attenuated macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1. Overexpression of PON2 protected against endoplasmic reticulum stress-induced apoptosis when the stress was induced by interference with protein modification but not when endoplasmic reticulum stress was induced by Ca2+ deregulation. SUMMARY: Both mouse and human studies have demonstrated the antioxidative and atheroprotective effects of PON1. The mechanisms by which PON2 exerts its atheroprotective effects are emerging. Large-scale epidemiologic studies are needed to further examine the relationship between PON2 genetic polymorphisms and risk for CVD. Elucidation of the physiologic substrates of the PON proteins is of particular importance to further advance this field. PMID- 19474730 TI - The glomerular filter: an imperfect barrier is required for perfect renal function. AB - PURPOSE OF REVIEW: There is currently a major debate on the mechanisms of albuminuria, and this review appraises recent studies in this area. RECENT FINDINGS: The traditional view of albuminuria is that it is the result of damage to an essentially impermeable glomerular barrier. However, over the years, critical evidence for this traditional model has been shown to be flawed. An alternative explanation has evolved in which the glomerular filter governs albumin permeability by size selectivity alone. This means that the filter offers a significant barrier to albumin, but it is imperfect - the barrier leaks albumin. The virtue of this leakage is that it endows the filter an in-built anticlogging mechanism. The filtered albumin, if not rescued, would be excreted at nephrotic levels in the urine. There is evidence that proximal tubular cells participate in retrieving most of this filtered albumin to return it back to the blood supply intact. A small amount of the filtered albumin is not retrieved but directed toward lysosomal degradation, and the peptide products are exocytosed into the tubular lumen and excreted. SUMMARY: In acquired and chemically induced kidney disease, albuminuria is the result of dysfunction in proximal tubular cell processing of albumin rather than alterations in glomerular permeability. PMID- 19474731 TI - Pendrin as a regulator of ECF and blood pressure. AB - PURPOSE OF REVIEW: Abnormal renal sodium handling plays a pivotal role in the pathophysiology of arterial hypertension. Though sodium is present in the diet as a chloride salt, most studies have focused on the renal mechanisms of sodium transport and their regulation, and very few have investigated the impact of chloride. However, strong evidence indicates that chloride may play a very important role in the 'prohypertensive' effects of sodium. RECENT FINDINGS: Several observations indicate that sodium has to be administered as NaCl and not as NaHCO3 to raise arterial blood pressure. Recently, genetic studies have pointed out the critical role of the most distal parts of the nephron in regulating sodium balance and blood pressure. Interestingly, in those segments, the transport of Na+ and Cl- proceeds separately, through different molecules. Recent evidence has demonstrated that an apical Cl-/HCO3- exchanger called pendrin is an absolute requirement for chloride reabsorption in the collecting system, indicating that chloride absorption is not passive and paracellular but is mediated by the intercalated cells. Importantly, pendrin disruption protects mice against mineralocorticoid-induced hypertension and impairs renal adaptation to a low NaCl diet. Moreover, recent findings suggest several mechanisms by which chloride transport might affect NaCl balance and blood pressure. SUMMARY: Pendrin mediated chloride transport through intercalated cells appears to be an independent and important determinant of renal NaCl handling and therefore might represent a new target for blood pressure control. PMID- 19474732 TI - An update on Stevens-Johnson syndrome and toxic epidermal necrolysis in children. AB - PURPOSE OF REVIEW: This study summarizes current research and understanding of the pathogenesis of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) and provides an update on the treatment of these conditions in children. RECENT FINDINGS: The association of specific human leukocyte antigen subtypes with SJS and TEN occurring in certain racial groups to specific drugs has led to recommendations on pretreatment testing. Several pathways have been postulated to lead to keratinocyte apoptosis in SJS and TEN. These include Fas-Fas ligand interaction, cytotoxic T-cell and natural killer-cell damage via perforin/granzyme B/granulysin and tumor necrosis factor-alpha. The use of intravenous immunoglobulins and systemic corticosteroids in TEN is still controversial, and more trials are needed to prove the efficacy of these agents. Newer agents such as cyclosporin, infliximab and plasmapheresis have shown promise in the treatment of SJS and TEN. SUMMARY: As the pathogenesis of SJS and TEN is further unraveled, the emergence of newer therapeutic agents with more specific mechanisms of action may lead to improved survival in this oftentimes devastating disease. PMID- 19474733 TI - Autoimmune thyroid disease: unlocking a complex puzzle. AB - PURPOSE OF REVIEW: The autoimmune thyroid diseases (AITD), Graves' disease and chronic lymphocytic thyroiditis (CLT) are amongst the most common endocrine diseases in childhood and adolescence. The application of molecular biology has permitted an unparalleled insight into susceptibility genes that predispose to their development and has allowed enhanced understanding of their complex immune pathophysiology. RECENT FINDINGS: The susceptibility genes that predispose to AITD can be subdivided into those that affect the immune response in general and thyroid-specific antigens. Both known and new susceptibility genes have been the focus of recent attention. Although there is no known human leukocyte antigen (HLA) association in CLT, recent work has demonstrated an association with a specific amino acid pocket signature irrespective of the HLA-DR class. In Graves' disease a specific combination of polymorphisms for thyroglobulin and HLA-DR markedly increases the odds ratio for developing disease. The availability of recombinant antigen [particularly thyroid peroxidase and thyrotropin (TSH) receptor] and of high affinity monoclonal antibodies has provided insight into the specific epitopes recognized by antibodies in AITD and has confirmed the increased affinity of stimulating TSH receptor antibodies for the shed A subunit rather than the holoreceptor. SUMMARY: Powerful molecular tools have been developed that have shed light on the nature of the susceptibility genes for and the pathophysiology of AITD. These have already led to improved diagnostic tools and, hopefully, will permit the development of more specific immune therapy in the future. PMID- 19474734 TI - Confidentiality, consent, and caring for the adolescent patient. AB - PURPOSE OF REVIEW: This study reviews the healthcare-related rationale for providing confidential care to adolescents, as well as the legal framework for the provision of such care. RECENT FINDINGS: Physician assurances of confidentiality increase adolescents' willingness to disclose sensitive health information, but these assurances are rarely given. Physicians may not be aware of legal minor consent guidelines or may be concerned about parental reaction to such confidential discussions. Fortunately, many parents and teens understand the importance of confidential healthcare. Adolescent consent and confidentiality laws vary from state to state, but there are federal guidelines and common law concepts that are applicable throughout the United States. The Health Insurance Portability and Accountability Act Privacy Rule also provides guidelines for confidential care to minors. Future challenges for adolescent confidentiality include ease of access to electronic medical records as well as patient (and/or parent)-controlled health records. SUMMARY: Confidentiality for adolescents has important implications for the quality provision of healthcare for this vulnerable population. Physicians and other healthcare providers must be aware of these health implications, as well as federal policies, common law, and their individual state's laws pertaining to this important topic. PMID- 19474735 TI - Development and validation of the University of Washington Clinical Assessment of Music Perception test. AB - OBJECTIVES: Assessment of cochlear implant outcomes centers around speech discrimination. Despite dramatic improvements in speech perception, music perception remains a challenge for most cochlear implant users. No standardized test exists to quantify music perception in a clinically practical manner. This study presents the University of Washington Clinical Assessment of Music Perception (CAMP) test as a reliable and valid music perception test for English speaking, adult cochlear implant users. DESIGN: Forty-two cochlear implant subjects were recruited from the University of Washington Medical Center cochlear implant program and referred by two implant manufacturers. Ten normal-hearing volunteers were drawn from the University of Washington Medical Center and associated campuses. A computer-driven, self-administered test was developed to examine three specific aspects of music perception: pitch direction discrimination, melody recognition, and timbre recognition. The pitch subtest used an adaptive procedure to determine just-noticeable differences for complex tone pitch direction discrimination within the range of 1 to 12 semitones. The melody and timbre subtests assessed recognition of 12 commonly known melodies played with complex tones in an isochronous manner and eight musical instruments playing an identical five-note sequence, respectively. Testing was repeated for cochlear implant subjects to evaluate test-retest reliability. Normal-hearing volunteers were also tested to demonstrate differences in performance in the two populations. RESULTS: For cochlear implant subjects, pitch direction discrimination just-noticeable differences ranged from 1 to 8.0 semitones (Mean = 3.0, SD = 2.3). Melody and timbre recognition ranged from 0 to 94.4% correct (mean = 25.1, SD = 22.2) and 20.8 to 87.5% (mean = 45.3, SD = 16.2), respectively. Each subtest significantly correlated at least moderately with both Consonant-Nucleus-Consonant (CNC) word recognition scores and spondee recognition thresholds in steady state noise and two-talker babble. Intraclass coefficients demonstrating test-retest correlations for pitch, melody, and timbre were 0.85, 0.92, and 0.69, respectively. Normal-hearing volunteers had a mean pitch direction discrimination threshold of 1.0 semitone, the smallest interval tested, and mean melody and timbre recognition scores of 87.5 and 94.2%, respectively. CONCLUSIONS: The CAMP test discriminates a wide range of music perceptual ability in cochlear implant users. Moderate correlations were seen between music test results and both Consonant-Nucleus-Consonant word recognition scores and spondee recognition thresholds in background noise. Test-retest reliability was moderate to strong. The CAMP test provides a reliable and valid metric for a clinically practical, standardized evaluation of music perception in adult cochlear implant users. PMID- 19474736 TI - Early suspension of activated protein C treatment in septic patients after shock reversal. AB - BACKGROUND AND OBJECTIVE: After observing that the interruption of activated protein C (aPC) treatment after septic shock reversal was not associated with any deleterious effect, we started to suspend the treatment whenever vasopressors were no longer required. We present a report of our data. METHODS: We studied retrospectively a 3-year septic shock database that included 157 patients from a surgical ICU in a university hospital. aPC was considered to be indicated in 111 cases. We analysed data from 20 surgical patients with septic shock in whom aPC treatment was suspended before 96 h due to noradrenaline withdrawal (NA-). These patients were compared with a group of patients in whom aPC was suspended for coagulation disorders or surgical reasons while still receiving vasopressor treatment (NA+, n = 11), with patients not treated with aPC, although presenting criteria for its use (aPC-, n = 31) and with patients receiving the standard protocol for 96 h (aPC+, n = 49). RESULTS: No differences in age, sex, severity scores or source of infection were found between groups. Noradrenaline was not required by any NA- patient within 24 h after aPC withdrawal. A statistically nonsignificant trend to a lower mortality was observed in the NA- patients [4/20 (20%) vs. 5/11 (46%) in NA+, 18/31 (58.1%) in aPC- and 22/49 (45%) in aPC+ patients, P = 0.066]. CONCLUSION: The use of aPC should be considered in septic shock, but its suspension after shock reversal in this small series of patients was not associated with any deleterious effect. PMID- 19474737 TI - Awake intubation with the Bonfils fibrescope in patients with difficult airway. AB - BACKGROUND: In the majority of patients with difficult airways intubated using the Bonfils fibrescope, intubations have been performed under general anaesthesia. Our aim is to report a consecutive series of intubations on awake patients with anticipated difficult airways, performed using the Bonfils fibrescope. METHODS: A prospective case series of intubations performed with the Bonfils fibrescope by a single anaesthesiologist is described in this article. Thirty patients with anticipated difficult airways were included (11 of them after failed intubations with Macintosh laryngoscope). Awake intubation attempts were performed under mild sedation and topical anaesthesia (with or without transcricothyroid membrane injection). The effectiveness was assessed in terms of success rate, number of attempts, difficulties, and complications encountered. RESULTS: Overall, awake intubation was successful in 29 out of 30 patients (96.6%). In the predicted difficult airway group, 19 patients with anticipated difficult airways were included. Awake intubation with Bonfils fibrescope was successful in 18 out of 19 patients (94.7%). In the known failed intubation group, 11 patients were included; the airways of five of them had already been managed with flexible fibrescope. All patients were successfully intubated awake with the Bonfils fibrescope. CONCLUSIONS: Our findings confirm that awake intubation with the Bonfils fibrescope is well tolerated and highly successful, even if performed by operators in training, and strengthen the evidence that the Bonfils fibrescope is one of the most promising devices to assist intubation in patients with difficult airways. PMID- 19474738 TI - Vitality and recurrent event risk in acute myocardial infarction survivors. AB - BACKGROUND: Low vitality, characterized by fatigue and lack of energy, is common among survivors of acute myocardial infarction (AMI) and has been shown to be associated with increased risk of primary and secondary cardiac events. The goal of this study was to determine whether an association between vitality and recurrent cardiac events (nonfatal MI, cardiac death) among acute MI survivors persists after controlling for possible physiological and psychological confounders. DESIGN AND METHODS: Incident AMI survivors (n = 1328) from Erie and Niagara (New York) county hospitals were enrolled and followed up to 9 years. Vitality was measured by the Short Form-36 on a 0-100 scale approximately 4 months post-AMI. Cox proportional hazards models were developed to assess the vitality-recurrent event association controlling for traditional cardiovascular disease risk factors, index MI severity, and psychological correlates of vitality. RESULTS: Low-vitality individuals at baseline were more likely females, of higher BMI, smoking, diabetic, less physically active, and to have worse depression scores. Vitality was not strongly associated with MI severity markers. Lower vitality scores were associated with increased risk of recurrent cardiac events: adjusted hazard ratios (95% CI) for vitality scores 51-79, 21-50, and < or =20 (compared with > or =80) were 1.2 (0.8, 1.8), 1.4 (0.9, 2.2), and 2.9 (1.5, 5.4), respectively (Ptrend = 0.005). CONCLUSION: Low vitality was associated with increased risk of recurrent cardiac events among AMI survivors after controlling for physiological and psychological confounders. Mechanistic links with vitality should be sought as interventional targets. PMID- 19474739 TI - Validity, prognostic value and optimal cutoff of respiratory muscle strength in patients with chronic heart failure changes with beta-blocker treatment. AB - BACKGROUND: Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on beta-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists. DESIGN: Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis. METHODS: In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26-75 months). RESULTS: Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879-0.975; chi(2): 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P=0.02, for patients not on BBL and 4.3 versus 16.2%, P<0.001, for patients on BBL. CONCLUSION: This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters. PMID- 19474740 TI - Ulcerative colitis in the Tuzla region of Bosnia and Herzegovina between 1995 and 2006: epidemiological and clinical characteristics. AB - BACKGROUND: Bosnia and Herzegovina (B&H) is one of the Eastern European countries that lacks data on the epidemiology of ulcerative colitis (UC). AIMS: We aimed to assess the epidemiological and clinical characteristics of UC in Tuzla Canton of B&H during a 12-year period (1995-2006). PATIENTS AND METHODS: We retrospectively evaluated hospital records of both UC inpatients and outpatients residing in Tuzla Canton of B&H (total of 496 280 inhabitants) between 1995 and 2006. Patients that firmly satisfied the diagnostic criteria for UC were included in the study. Incidence rates were calculated with age standardization using European population standards. Trends in incidence were evaluated as moving 3 year averages. RESULTS: During the observed period, 214 patients met the diagnostic criteria for UC. The average age-standardized incidence was found to be 3.43/10 inhabitants [95% confidence interval (CI) = 2.97-3.89], ranging from 0.22 to 7.44 per 10. The mean annual crude incidence in the last 5 years of study (2002-2006) was 5.55/10 (95% CI = 4.63-6.48). The prevalence of UC during the observed period was found to be 43.1/10 (95% CI = 37.3-48.8). The incidence of UC increased dramatically from the average of 1.01/10 in the period between 1995 and 1997 to 6.04/10 between 2004 and 2006, as did the number of colonoscopies performed, from 29 in 1995 to 850 in 2006. The average yearly incidence of confirmed UC cases detected on colonoscopy was 5.56 per 100 colonoscopies per year (95% CI = 4.81-6.30) and only 3.92 per 100 colonoscopies (95% CI = 3.26 4.57) in the last 5 years of the observed period. CONCLUSION: Tuzla Canton of B&H is a region with an increasing incidence of UC, which is most likely a direct consequence of a wider use of colonoscopy. We believe that in the next few years, the incidence of UC in this region will probably reach the annual incidence rate of 6 per 10 inhabitants. PMID- 19474741 TI - Is splenectomy a treatment option for aseptic abscesses in patients with Crohn's disease? AB - The most common extraintestinal manifestations of Crohn's disease concern joints, skin, and eyes; however other organs such as liver, pancreas, kidneys, heart, lungs or brain can also be affected. Aseptic abscesses are an emergent entity in patients with inflammatory bowel disease and despite medical treatment the surgical approach may represent an alternative therapy. We report a case of a young woman with splenic aseptic abscesses as complication of Crohn's disease. After steroid sparing and antibiotic failure the patient underwent successful splenectomy. PMID- 19474742 TI - Serum concentrations of human angiopoietin-like protein 3 in patients with nonalcoholic fatty liver disease: association with insulin resistance. AB - OBJECTIVE: Insulin resistance is considered a key feature of nonalcoholic fatty liver disease (NAFLD). In this setting, experimental studies have suggested a potential role of angiopoietin-like (ANGPTL) proteins in the pathogenesis of hepatic steatosis and the metabolic syndrome. In this study, we sought to investigate the plasma levels of ANGPTL protein 3 (ANGPTL3)--a liver-derived protein that modulates plasma triglyceride clearance--in patients with definite nonalcoholic steatohepatitis (NASH, n=40), borderline NASH (n=8), simple fatty liver (n=9), and healthy controls without evidence of liver disease (n=14). METHODS: Levels of ANGPTL3 were measured by enzyme-linked immunosorbent assay and compared in the four study groups. Moreover, concentrations of ANGPTL3 were assessed in relation to the general characteristics of the study participants and the results of liver biopsy. RESULTS: Levels of ANGPTL3 were significantly higher in patients with definite NASH (389+/-110 ng/ml, P<0.05) and borderline NASH (433+/-70 ng/ml, P<0.05) compared with controls (291+/-78 ng/ml). No significant differences were found in patients with simple fatty liver (321+/-119 ng/ml) as compared with controls. In correlation analyses of the entire study cohort, ANGPTL3 was significantly and positively associated with homeostatic model assessment for insulin resistance (r=0.28, P<0.05) but not with histological staging and pathological characteristics of NAFLD. CONCLUSION: Although subject to future confirmation, our data suggest that ANGPTL3 levels are elevated in the more severe forms of NAFLD and could be associated with insulin resistance in this setting. PMID- 19474743 TI - Management of gastroesophageal reflux disease in primary care settings in Spain: SYMPATHY I study. AB - OBJECTIVE: Our study was designed to assess the symptom loads, treatment strategies, and impact on daily life of patients with gastroesophageal reflux disease (GERD) symptoms who consulted primary care (PC) health care providers in Spain. METHODS: This was a multicenter, observational, cross-sectional study in a sample of 5735 consecutive patients visiting PC clinics with GERD symptoms. Participating primary care physicians (PCPs) collected clinical data by using a questionnaire, and completed a survey on their perceptions of diagnostic and therapeutic approaches to GERD. Patients self-completed the GERD Impact Scale during the study visit. RESULTS: In the week before visiting the PC clinic, typical GERD symptoms were present in a majority of patients (89.6% heartburn and 81.6% regurgitation), but extraesophageal symptoms were also frequent (55.6% reflux-related sleep disturbances, 45.7% noncardiac chest pain, 30.8% chronic cough, and 24.7% hoarseness), these being more prevalent in the patients diagnosed earlier. Although primary care physicians considered that 55.9% of the patients could be diagnosed on the basis of symptoms without further investigation, in their practice only one-third of new diagnoses of GERD and 71.1% of those already diagnosed were symptom-managed. Upon arrival at the clinic, patients with GERD symptoms were taking the following medications: 28.1% (47.8% in the case of those already diagnosed) proton pump inhibitors (PPIs), 16.6% antacids, 6.1% H2 antagonists, and 4.5% prokinetics. Most patients (90.2%) were treated with PPIs after the study visit. The evaluation of agreement between physicians and patients on the severity of GERD resulted in a kappa index of 0.19. CONCLUSION: There is a high occurrence of typical and extraesophageal symptoms in patients in Spain complaining of GERD symptoms in PC settings. Two thirds of new GERD patients were referred for further investigation. PPIs were the treatment prescribed in almost all cases. The degree of agreement between physicians and patients about the severity of the symptoms was limited. PMID- 19474744 TI - HLA class II polymorphism in children with coeliac disease in Tunisia: is there any influence on clinical manifestation? AB - OBJECTIVE: To elucidate the HLA DRB1, DQB1 and DQA1 polymorphism in Tunisian children with typical form of coeliac disease (CD) in comparison with those from mass screening (atypical and silent CD). MATERIALS AND METHODS: We recruited three groups: group I: 40 CD children diagnosed according to the ESPGHAN criteria. group II: 40 healthy controls matched with sex, age and geographic origin. group III: 38 CD children coming from mass screening in schoolchildren. HLA class II DRB1, DQB1 and DQA1 alleles were typed by PCR-sequence-specific primer. RESULTS: Comparing the groups I and II, we found a pronounced increase of the susceptible alleles HLA DRB1*03 (relative risk, RR = 4.18, Pc = 0.001), DQB1*02 (RR = 7.9, Pc<0.0001) and DQA1*0501 (RR = 4.1, Pc = 0.001). As for protective alleles, we detected a high frequency of DRB1*13 (RR = 0.059, Pc = 0.001), DQA1*0102 (RR = 0.071, Pc = 0.009) and DQB1*06 (RR = 0.125, Pc = 0.0042). Haplotype analysis showed that the main combination observed was the conformation of DQ2 (DQA1*0501-DQB1*02) in 36 patients from group I and 30 from group III. There was no statistically significant difference between the groups I and III according to the distribution of the different alleles. CONCLUSION: We confirmed in this study the high frequency of DQ2 haplotype in CD patients and we identified new protective alleles DRB1*13, DQA1*0102 and DQB1*06. However, HLA polymorphism seems to have no evident impact on clinical outcome of CD. PMID- 19474745 TI - Peginterferon alpha-2b and ribavirin for the treatment of chronic hepatitis C in Japanese pediatric and young adult patients: a survey of the Japan Society of Pediatric Hepatology. AB - OBJECTIVES: Only a few studies on the treatment with peginterferon-2b and ribavirin are available in children with chronic hepatitis C virus (HCV). The aim of this study was to evaluate both the efficacy and the safety of the treatment in Japanese children and young adults. METHODS: Twenty-two of 41 members of the Japan Society of Pediatric Hepatology reported on 37 cases who were treated with peginterferon and ribavirin. RESULTS: Of the 37 patients, 29 have completed the treatment and all of them cleared the HCV virus. Three patients are still being treated, whereas the remaining five failed to complete the treatment. Cessation of the treatment was because of the nonresponsiveness (n=3), the expense of the treatment (n = 1), or lethargy (n=1). After excluding the three patients, who were continuing the treatment and one who has not completed the 24-week follow-up period, from the 37 patients, 33 were available for sustained virologic response (SVR) analysis. After 4 weeks of follow-up, one of the 33 relapsed. An intention to-treat analysis showed that 27 of the 33 (81.8%) achieved a SVR. The only factor significantly associated with SVR was their virologic response status at week 4. CONCLUSION: The results showed that the present patients infected with HCV and treated with peginterferon-2b and ribavirin achieved a remarkably high SVR rate. In addition, most of the patients achieved a SVR once they showed a virologic response at week 4. The combination of peginterferon-alpha with ribavirin may be considered as a standard therapy for children and young adults. PMID- 19474747 TI - A Greek survey of community prevalence and characteristics of constipation. AB - OBJECTIVES: We evaluated the prevalence and the main characteristics of constipation in the Greek general population. METHODS: The study sample included 1000 individuals, 15-64-years-old, who were citizens of Athens, Thessaloniki, or one of 11 Greek cities with a population of greater than 10 000, and the sample was selected by a stratified, multistage, random sampling procedure. Questionnaires were completed for each individual by personal interviews. RESULTS: The prevalence of self-reported constipation within the last year was 14%, whereas another 2% of participants had constipation according to the Rome III criteria. Constipation was significantly less frequent in males than females (11 vs. 21%, P<0.001), younger individuals (15-29-years-old: 12%, 30-59-years old: 17%, 60-64-years-old: 25%, P = 0.006) and citizens of Athens than in citizens of other Greek cities (19 vs. 13%, P = 0.008). The mean duration of constipation was 6.3 years (females: 6.9, males: 5.1) and its mean frequency was once per 4 days. Constipation was considered to be mostly because of inappropriate diet (51%), stress (30%), and absence of physical activity (19%). Constipated patients mainly used dietary modifications (48%) and/or traditional products (40%), and/or laxatives (48%), whereas 19% of them did not try to treat constipation. CONCLUSION: Constipation is present in approximately 15% of the Greek general population being significantly more frequent in females and older age individuals. Current dietary habits, stress, and the way of living seem to be considered as its most common causes. Although the duration is usually long, a substantial proportion of constipated patients do nothing to treat the problem, whereas the majority of them use dietary modifications and/or traditional products without satisfactory results. PMID- 19474746 TI - The in-vivo effect of pyrrolidine dithiocarbamate on hepatic parenchymal microcirculation and oxygenation of the rat liver. AB - OBJECTIVE: Pyrrolidine dithiocarbamate has been shown to be a potent inducer of haemeoxygenase-1. This study investigated its in-vivo effects on systemic and hepatic microcirculatory perfusion. METHODS: Male Sprague-Dawley rats (n=12) were administered intravenously with pyrrolidine dithiocarbamate (10, 20 and 50 mg/kg body weight) or vehicle (0.2 ml physiological saline) served as control. Systemic and hepatic haemodynamics including arterial oxygen saturation, heart rate, mean arterial blood pressure and portal blood flow were monitored. Microcirculation in skeletal muscle and liver was measured by laser Doppler flowmetry and intravital fluorescence microscopy, whereas hepatic tissue oxyhaemoglobin and cytochrome oxidase CuA redox state, which is an indicative of extracellular and intracellular oxygenation were measured by near infrared spectroscopy. RESULTS: Pyrrolidine dithiocarbamate induced a dose-dependent increase in mean arterial blood pressure and skeletal muscle microcirculation. The hepatic parenchymal microcirculation was significantly improved and an increase in sinusoidal diameter and reduction in RBC velocity were observed. Pyrrolidine dithiocarbamate also showed beneficial effect on hepatic tissue oxygenation showed by an increase in oxyhaemoglobin and cytochrome oxidase CuA redox state as well. CONCLUSION: Pyrrolidine dithiocarbamate improves hepatic parenchymal microcirculation and tissue oxygenation, suggesting that it may be used as a potential agent in pharmacological preconditioning in the liver. PMID- 19474748 TI - Germline mutation of the E-cadherin gene in three sibling cases with advanced gastric cancer: clinical consequences for the other family members. AB - BACKGROUND AND AIMS: Germline mutations in the E-cadherin (CDH1) gene have been found in families with hereditary diffuse gastric cancer (HDGC). These families are characterized by a highly penetrant susceptibility to diffuse gastric cancer with an autosomal dominant pattern of inheritance. We describe the clinical presentation of three sibling cases with advanced gastric cancer, the way of confirming the suspicion of underlying HDGC and the clinical management of the other healthy family members. METHODS: Screening for CDH1 germline mutation was carried out by denaturing high-performance liquid chromatography and automated DNA sequencing. The clinical suspicion of HDGC has been confirmed by identifying a frameshift mutation in exon 9 (1302_1303insA, 1306_1307delTT) of the E-cadherin gene. RESULTS: Eight of nine tested family members were positive for the CDH1 germline mutation. Prophylactic laparoscopic gastrectomies were performed in five mutation carriers. After pathological examination, we could identify intramucosal malignant signet-ring cell carcinoma in all resected stomachs. CONCLUSION: This report underlines that prophylactic gastrectomy remains the only option to eliminate the high risk for gastric cancer in CDH1 mutation carriers. PMID- 19474749 TI - Pancreatic tuberculosis mimicking pancreatic carcinoma: series of three cases. AB - Tuberculosis (TB) is a worldwide pandemic, and is seeing a resurgence because of the AIDS epidemic. Pancreatic involvement is rare in the world, and when it is isolated around the pancreas, it is often mistaken for pancreatic carcinoma. We report three cases of pancreatic TB that masqueraded as malignancy in a 50-year old female, a 34-year-old male and a 39-year-old male with a previous history of abdominal TB. All had computed tomographic scans suspicious of possible pancreatic malignancy. Endoscopic ultrasound was performed in two patients. Two patients underwent laparotomy but did not undergo the intended pancreaticoduodenectomy, whereas the third patient was diagnosed after computed tomographic-guided percutaneous biopsy of the pancreatic mass. In conclusion, pancreatic TB should always be considered as a differential diagnosis to pancreatic malignancy. PMID- 19474750 TI - Trends in incidence of oesophageal and stomach cancer subtypes in Europe. AB - OBJECTIVE: Time trend studies in the USA have shown that the incidences of adenocarcinomas of the oesophagus and gastric cardia have risen strongly since the 1970s, whereas the incidence of squamous cell carcinomas of the oesophagus has declined. Earlier, we found that the incidence of these adenocarcinomas also rose in some European countries until the early 1990s. The main goal of this study was to investigate more recent trends in the incidence of oesophageal and stomach cancer subtypes in the European countries. METHODS: Eurocim cancer incidence data of 23 cancer registries from 13 European countries were used to investigate the incidence trends in oesophageal and stomach cancer subtypes during the 1983-1997 period. We calculated estimated annual percentage changes (EAPCs) in European age-standardized incidence rates and 95% confidence intervals. RESULTS: The incidence of adenocarcinomas of the oesophagus and gastric cardia rose in most, but not all, registration areas (EAPCs were usually 1-7%), the strongest in the UK and Ireland. Oesophageal squamous cell carcinoma incidence rose mostly in Northern European and Slovakian men (EAPCs: 1-5%) and in women from all regions (EAPCs: 1-8%), but declined mostly in Southern and Western European men (EAPCs: -1 to -5%). CONCLUSION: Our results are partly in line with earlier findings on adenocarcinomas of the oesophagus and gastric cardia. There was, however, substantial heterogeneity in trends of subtypes of these cancers within Europe. There may be different risk factors for these cancers, and the prevalence of these risk factors may differ among countries. PMID- 19474752 TI - Comparison of subjective grading of limbal redness by eyecare practitioners in three countries. AB - OBJECTIVES: To compare grading of a biomicroscopy sign between eye care practitioners in three countries of widely different geographies-the United States, Australia, and Germany-and to test the accuracy of grading the sign within each country. METHODS: Four eye care practitioners licensed in the practice of optometry in each country were sent sets of limbal redness images that were printed from the Efron Grading Scale morphing program. Each set consisted of 18 images randomly selected over the range of 0 to 4, inclusive. Each image was printed on a separate page with the grade scale from 0 to 4 with 0.5 steps. Each practitioner received the same set of images that were packaged in random order. Seventy-two (72) grades were collected from each country, which exceeded the sample size estimates for both the between and within country objectives. RESULTS: No statistically significant differences were found between countries for pairwise comparisons (P<0.02, McNemar test, adjusted for multiple comparisons). No statistically significant differences were found within each country between observed and expected values for grades from Germany and Australia (P>0.05, chi test); however, a statistically significant difference was found for the United States (P<0.05, chi test). CONCLUSIONS: These findings support the generalization of results of limbal redness grades from trials that are conducted in several countries or in one country and used in another, i.e., practitioners may expect similar findings for this sign among their patients no matter which of their colleagues are investigators. They also indicate that different strategies for grading limbal redness may exist among practitioners in the countries tested. Study sponsors may want to include standardized training for investigators. PMID- 19474751 TI - Prevalence of contact lens-related complications: UCLA contact lens study. AB - PURPOSE: This study is a cross-sectional analysis of the types and prevalence of contact lens (CL)-related complications among CL wearing patients seen in a university clinic setting. METHODS: Data on CL material and design, care system, and ocular complications were recorded and statistically analyzed for CL wearers. RESULTS: Of the 572 patients (846 eyes) recruited during the study, approximately 50% of the eyes had at least one CL-related complication. Rigid gas permeable (GP) CLs had a statistically lower (P<0.01) average number of complications (0.54 +/- 0.68) than soft contact lenses (SCLs) (0.85 +/- 0.82). Papillae and giant papillary conjunctivitis were the most prevalent complications in both GP and SCL wearers. Silicone SCLs (0.79 +/- 0.76) had a slightly lower, although not statistically different (P=0.23), rate of complication than nonsilicone SCLs (0.90 +/- 0.87). Although not statistically significant (P=0.29), extended wear CL use had a higher complication rate (0.93 +/- 0.84) compared with daily wear (0.73 +/- 0.79). Use of "other" solution, including generic and private label solutions, had the highest rate of complications for both SCLs (1.11 +/- 1.27) and GPs (0.96 +/- 0.93) compared with name brand solutions. CONCLUSIONS: The prevalence of CL-related complications, regardless of lens design, material, and wear modality, highlights the importance of early detection with appropriate professional management and treatment. PMID- 19474753 TI - Evaluation of the role of ProKera in the management of ocular surface and orbital disorders. AB - OBJECTIVES: To report the efficacy and safety profile of sutureless and adhesiveless amniotic membrane device (ProKera, Bio-Tissue, Inc., Miami, FL) in the management of various ocular surface and orbital disorders. METHODS: Twenty eyes of 20 patients underwent placement of 21 ProKera implants between March 2006 and July 2007 at the University of Texas Southwestern Medical Center. Patient demographics, indications for placement, and duration of ProKera retention were recorded. Outcomes measured included corneal epithelial healing, visual acuity, patient tolerance, and adverse events. RESULTS: ProKera was most commonly used in patients with corneal neovascularization with or without limbal stem-cell deficiency (10 eyes). Other indications included recurrent pterygium or pseudopterygium (three eyes), anophthalmic orbit contraction (two eyes), persistent epithelial defects (two eyes), severe thinning in a corneal ulcer (one eye), benign hereditary intraepithelial dyskeratosis (one eye), and band keratopathy (one eye). The mean duration of ProKera retention was 25.3 days (range, 0-125) visual acuity improved in 12 eyes (60%). Immediate adverse events included residual epithelial defects after removal (five eyes) and spontaneous extrusion of the implant (four eyes). Six patients (30%) reported eye pain or headache and four eyes (20%) had recurrence of the primary pathology. CONCLUSIONS: Sutureless and adhesiveless amniotic membrane transplantation is a safe and effective method to promote healing and reconstruction of the ocular surface and orbit with minimal side effects. Recurrence of the underlying primary pathology remains a concern. The advent of a newer, softer conformer ring may improve patient tolerability and limit discomfort. PMID- 19474754 TI - Antidepressive-drug-induced bodyweight gain is associated with polymorphisms in genes coding for COMT and TPH1. AB - Bodyweight gain is a common side effect of treatment with antidepressive drugs; however, little is known about the mechanisms behind this weight gain. Genetic differences may contribute to the susceptibility for bodyweight gain during antidepressive treatment. The objective of this study was to examine the association of antidepressive-drug-induced bodyweight gain with polymorphisms in genes within the serotonin or catecholamine systems. Participants (N = 165) were selected from the Danish Psychiatric Central Research Register from June 2005 through May 2007 as patients with a diagnosis of a single depressive episode and who were under antidepressive treatment. Weight gainers were identified based on rating with the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. Polymorphisms in catechol-O-methyltransferase, tryptophan hydroxylase (TPH1), serotonin receptor 2C (HTR2C) and serotonin transporter (SLC6A4) genes were identified and associated with bodyweight gain during treatment. The AG genotype of catechol-O-methyltransferase rs4680 and the AA genotype of TPH1 rs18532 were significantly associated with bodyweight gain during antidepressive treatment, when adjusted for age and sex. These new findings may aid the understanding of susceptibility to side effects such as weight gain during clinical antidepressive treatment. PMID- 19474756 TI - Prevalence of cervical cancer screening of HIV-infected women in the United States. AB - BACKGROUND: HIV-infected women are at increased risk of cervical cytologic abnormalities. HIV treatment guidelines recommend annual Papanicolaou (Pap) tests for HIV-infected women. We assessed screening prevalence and associated factors among HIV-infected women. METHODS: We used data collected during 2000-2004 in an interview study of HIV-infected persons in 18 states. We performed logistic regression to describe factors associated with not having an annual Pap test. RESULTS: Of 2417 women, 556 (23.0%) did not report receiving a Pap test during the past year. Not having a Pap test was associated with increasing age [adjusted odds ratio (AOR) = 1.3 per 10 years, 95% confidence interval (CI): 1.1 to 1.4] and most recent CD4 count of <200 cells per microliter (AOR = 1.6, CI: 1.1 to 2.1) or unknown (AOR = 1.4, CI: 1.1 to 1.7; both vs. CD4 count of >or=200 cells/microL). Odds of a missed Pap test increased for women whose most recent pelvic exam was not performed at their usual source of HIV care (AOR = 2.6, CI: 2.1 to 3.2). CONCLUSIONS: Nearly 1 in 4 women did not receive an annual Pap test. HIV care providers should ensure that HIV-infected women receive annual Pap tests, recognizing that missed Pap tests are more likely among older women and women with low CD4 cell counts. Integrating HIV and gynecologic care and educating clinicians about recommendations may increase screening. PMID- 19474758 TI - Recurrent ventricular fibrillation due to coronary artery spasm immediately after ascending aorta replacement. AB - Coronary artery spasm (CAS) is a dangerous complication during cardiac surgery, causing arduous weaning of extracorporeal circulation (ECC) and myocardial tissue loss with consequent left and right ventricular dysfunctions. We describe the case of a 67-year-old man with hypertension and smoking habit, with ECG evidence of lateral myocardial ischemia without symptoms. On this basis, he was investigated with scintigraphy, which confirmed an anterior-lateral area of reversible ischemia and, subsequently, with angiography, which revealed just mild lesion (50%) of diagonal ramus associated with ascending aorta aneurysm: no sign of CAS was detected. Left ventricular function was normal, with mild hypokinesia of the apical segments and trivial aortic regurgitation. The patient underwent ascending aorta replacement with arduous ECC weaning due to CAS: exclusively, the use of intravenous administration of diltiazem led to the solution of this complication. Even if medical therapy is generally efficacious for this complication, the diagnosis is very complicated when it appears in the operating room immediately after cardiac surgery because of the lack of any useful device. The difficulty of diagnosis in the operating room might compromise patient outcome. In our opinion, when ECC weaning is complicated by several episodes of malignant tachyarrhythmia and there is the suspicion of underlying ischemic cause without other obvious causes, CAS must be considered and empirical therapy with calcium channel blockers should be used. PMID- 19474757 TI - Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. AB - BACKGROUND: There are limited data on the risk of developing HIV drug resistance based on the CD4 cell count at which highly active antiretroviral therapy (HAART) is initiated. METHODS: We examined data from participants in the HIV Outpatient Study who initiated antiretroviral therapy with HAART in 1999 or later (when genotypic resistance testing became more commonly used in clinical practice and in the HIV Outpatient Study), achieved virologic suppression, and subsequently experienced virologic failure and received a genotypic assay for antiretroviral resistance mutations. We assessed the frequency of resistance mutations at virologic failure and the differences in the frequencies of mutations by the CD4 stratum at which HAART was initiated using the Cochran-Armitage exact test. RESULTS: Of 683 patients who achieved virologic suppression on a first HAART regimen, 243 had virologic failure and 78 of these had a genotype resistance test done. Among these patients, the frequency of any HIV resistance mutations was 50% among patients who started HAART at 0-199 CD4 cells per cubic millimeter or 200 349 CD4 cells per cubic millimeter compared with 22% among patients who started HAART at >or=350 CD4 cells per cubic millimeter (P = 0.062). The frequency of nucleoside reverse transcriptase inhibitor-associated mutations was 48%, 31%, and 11% among persons who initiated nucleoside reverse transcriptase inhibitor containing HAART within these respective CD4 cell count strata (P = 0.005). We observed similar trends for nonnucleoside reverse transcriptase inhibitor associated (P = 0.040) and protease inhibitor-associated (P = 0.063) mutations among persons initiating HAART containing these agents. CONCLUSIONS: Patients failing HAART that was initiated at <350 CD4 cells per cubic millimeter had higher frequencies of resistance mutations to the classes of antiretrovirals to which they had been exposed than failing patients who initiated at >or=350 CD4 cells per cubic millimeter. Initiating HAART at higher CD4 cell counts may decrease the risk of developing treatment-limiting antiretroviral resistance. PMID- 19474755 TI - Uncontrolled viral replication as a risk factor for non-AIDS severe clinical events in HIV-infected patients on long-term antiretroviral therapy: APROCO/COPILOTE (ANRS CO8) cohort study. AB - OBJECTIVE: To determine risk factor for non-AIDS severe clinical events in HIV infected patients on long-term combination antiretroviral therapy (cART). METHODS: A validation committee reviewed each severe clinical event that occurred in the APROCO/COPILOTE (ANRS CO8) cohort that enrolled 1281 patients in 1997-1999 at the initiation of cART containing protease inhibitor. Probability of the occurrence of a first non-AIDS, cART-related, and AIDS-defining event was estimated, and potential determinants were studied using Cox regression models. RESULTS: During a median follow-up of 7.3 years, the incidence of non-AIDS events was higher than that of cART-related and AIDS-defining events (10.5, 3.6, and 2.6 per 100 patient-years, respectively). Bacterial (mainly airway) infections were the most frequent non-AIDS events (23.4%) followed by non-AIDS-defining malignancies and cardiovascular events (both 9.5%). Factors independently associated with the occurrence of a first non-AIDS event were age >60 years [hazard ratio (HR) 2.1; 95% confidence interval (CI): 1.3 to 3.2] and CD4 <100 cells per milliliter (HR 2.5; 95% CI: 1.8 to 3.6) but also plasma HIV RNA >4 log10 copies per milliliter at the time of the event (HR 1.9; 95% CI: 1.5 to 2.5). CONCLUSION: Optimization and permanent continuation of long-term antiretroviral therapy in HIV-infected patients is the best strategy to prevent or reduce the occurrence of non-AIDS severe morbidity. PMID- 19474759 TI - Stentless aortic valve implantation in heavily calcified aorta. AB - Two male patients who underwent an aortic valve replacement are presented in this study. After assessment, an aortic valve stenosis was diagnosed in both patients, and a multislice computed tomography scan confirmed the heavily calcified aorta and severe aortic stenosis. The computed tomography scan demonstrated the huge calcium deposits and their distribution in detail. Notably, the ascending aorta in both patients was severely plaqued, and only the supra-annular zone was free from any detectable calcium deposits. We present the images of this case and the surgical technique applied in this matter. PMID- 19474760 TI - Natural history of dilated cardiomyopathy: from asymptomatic left ventricular dysfunction to heart failure--a subgroup analysis from the Trieste Cardiomyopathy Registry. AB - BACKGROUND: Few data are available in the literature regarding the characteristics and prognosis of asymptomatic patients with idiopathic dilated cardiomyopathy (DCM). AIM: To determine the frequency with which patients affected by DCM are diagnosed in the asymptomatic state as well as to evaluate the natural history of such patients and the factors influencing their outcome. Moreover, we sought to compare the outcome of asymptomatic patients with that of patients with signs of overt heart failure at the time of first evaluation. METHODS AND RESULTS: We analyzed the data of 747 patients with DCM enlisted in the Heart Muscle Disease Registry of Trieste from 1978 to 2007. We divided our population into four groups; group 1 comprised 118 asymptomatic [New York Heart Association (NYHA) I] patients without a history of congestive symptoms (16%), group 2 comprised 102 asymptomatic (NYHA I) patients (14%) with a positive anamnesis for heart failure stabilized in medical therapy, group 3 comprised 327 patients (44%) with signs of mild heart failure (NYHA II) and group 4 comprised 200 patients (26%) in NYHA III-IV. During the follow-up of 112+/-63 months, 46 (21%) of 220 asymptomatic patients with DCM died or underwent heart transplantation. By Cox proportional model, left ventricular ejection fraction of 30% or less was a unique independent predictor either for death/heart transplantation (hazard ratio 3.15, 95% confidence interval 1.5-6.7, P=0.003) or for sudden death/major ventricular arrhythmias (hazard ratio 3.9, 95% confidence interval 1.7-9.3, P=0.002). Patients from group 1 had a trend for a better outcome with respect to those from group 2 (P=0.06). In comparison with the asymptomatic patients, those with signs of overt heart failure at baseline had a worse prognosis. CONCLUSION: The proportion of asymptomatic patients with DCM at the moment of first evaluation at our center is significant (30%). Among them, those without a previous history of heart failure had a less advanced disease and a trend for a better long-term outcome on optimal medical treatment. Therefore, early diagnosis may offer better long-term quality of life and even better survival. Further studies on larger populations are indicated. PMID- 19474761 TI - Electronic monitoring of patient adherence to oral antihypertensive medical treatment: a systematic review. AB - Poor patient adherence is often the reason for suboptimal blood pressure control. Electronic monitoring is one method of assessing adherence. The aim was to systematically review the literature on electronic monitoring of patient adherence to self-administered oral antihypertensive medications. We searched the Pubmed, Embase, Cinahl and Psychinfo databases and websites of suppliers of electronic monitoring devices. The quality of the studies was assessed according to the quality criteria proposed by Haynes et al. Sixty-two articles were included; three met the criteria proposed by Haynes et al. and nine reported the use of electronic adherence monitoring for feedback interventions. Adherence rates were generally high, whereas average study quality was low with a recent tendency towards improved quality. One study detected investigator fraud based on electronic monitoring data. Use of electronic monitoring of patient adherence according to the quality criteria proposed by Haynes et al. has been rather limited during the past two decades. Electronic monitoring has mainly been used as a measurement tool, but it seems to have the potential to significantly improve blood pressure control as well and should be used more widely. PMID- 19474762 TI - Coupling factor 6-induced prostacyclin inhibition is enhanced in vascular smooth muscle cells from spontaneously hypertensive rats. AB - OBJECTIVES: Coupling factor 6 (CF6) attenuates the endothelial generation of prostacyclin. However, the role of CF6 in the resistance arteriole that is directly related to vascular tone is not determined yet. We investigated the effect of endogenous and exogenous CF6 on prostacyclin generation in cultured vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: We cultured resistance arteriole VSMCs from the mesenteric artery network of spontaneously hypertensive rats (SHRs, n = 8) and Wistar-Kyoto rats (WKY, n = 8) by enzymatic method. The gene expression of CF6 was higher by 76 +/- 24% in SHR-derived VSMCs compared with WKY rat-derived VSMCs (P < 0.05) concomitant with the reduced degradation rate of CF6 mRNA. The release of CF6 in SHRs was higher than that in WKY rats (11.0 +/- 0.8 vs. 3.8 +/- 0.4 pg/microg protein, P < 0.05). Prostacyclin generation was attenuated in mesenteric arteriolar VSMCs from SHRs compared with those from WKY rats, but it was restored by neutralization of CF6 with its antibody. Exogenous administration of CF6 suppressed arachidonic acid release in a dose-dependent manner, and it was greater in SHRs than in WKY rats. Pretreatment with PP1, an inhibitor of tyrosine kinase c-Src, or receptor blockers such as ADP, efrapeptin, and an antibody to beta-subunit of ATP synthase blocked CF6-induced decrease in prostacyclin generation. CONCLUSION: These data suggest that CF6 suppresses prostacyclin generation in resistance arteriole VSMCs in an autocrine or paracrine fashion, and it is enhanced in SHRs by the overproduction of CF6 and the hyperresponsiveness to CF6. PMID- 19474763 TI - The global cost of nonoptimal blood pressure. AB - OBJECTIVE: Suboptimal blood pressure including established nonoptimal blood pressure has been shown to have significant economic consequences in developed countries. However, no exhaustive study has been done to evaluate its potential costs, globally. We, therefore, set out to estimate the global economic cost of nonoptimal blood pressure. METHODS: Estimates for healthcare costs attributed to suboptimal blood pressure for those over the age of 30 were made for all the World Bank regions. Annual and 10-year estimates using Markov models were made for the cost of treating nonoptimal blood pressure and its main sequelae: stroke and myocardial infarction. RESULTS: Suboptimal blood pressure cost US$370,000,000,000 globally in 2001. This represents about 10% of the world's overall healthcare expenditures. In the Eastern Europe and Central Asia region, high blood pressure consumed 25% of all health expenditures. Over a 10-year period, elevated blood pressure may cost nearly $1,000,000,000,000 globally in health spending, if current blood pressure levels persist. Indirect costs could be as high as $3,600,000,000,000 annually. CONCLUSION: Suboptimal blood pressure is responsible for a large and an increasing economic and health burden in developing countries. Although the majority of the current absolute expenditure occurs in the high-income countries, an ever-increasing proportion of the cost is going to be carried by developing countries. PMID- 19474764 TI - Work productivity impairment from musculoskeletal disorder pain in long-term caregivers. AB - OBJECTIVES: To examine the impact of Musculoskeletal Disorder (MSD) pain on work productivity in Long-Term Caregivers. METHODS: An eight item work productivity impairment scale specific to MSD pain was constructed, evaluated and used as part of a telephone survey of LTCaregivers health. RESULTS: The productivity impairment scale demonstrated good reliability and validity. The fifty-six of 71 caregivers (79%) reporting work-related MSD pain endorsed, on average > three of eight items in the impairment scale. Only two variables predicted productivity impairment: 1) pain frequency and 2) frequency of resident lifts and transfers. CONCLUSIONS: Specifically linking MSD pain from manual resident lifting to impaired work productivity may provide employers with additional visible impact of manual lifting beyond compensation costs alone, and thus promote adoption of safer lifting practices. PMID- 19474766 TI - Modulation of the motor area activity during observation of a competitive game. AB - Watching competitive games is a pervasive entertainment in humans and likely to be facilitated by our social cognitive abilities. We investigated the brain activity during observation of a competitive game by using near-infrared spectroscopy. The result showed that activity in the motor area was significantly greater when the individual's favored player won, compared with when the same player lost. The motor area was also activated when the individuals themselves performed the same action, showing the mirror neuron system property. Our results first showed that the motor area activity during observation of competitive games was modulated by the outcome of the game. We suggest that the observer's brain is more likely to share the winner's internal motor representation than that of the loser. PMID- 19474765 TI - MicroRNAs in the pathogenesis of Lung Cancer. AB - Lung cancer is the leading cause of cancer related deaths in the United States. It is estimated that in 2008 there were 215,000 new diagnoses of lung cancer and 163,000 deaths. Despite emerging technologies for potential early diagnosis and discovery of novel targeted therapies, the overall 5-year survival remains a disappointing 15%. Explanations for the poor survival include late presentation of disease, a lack of markers for early detection, and both phenotypic and genotypic heterogeneity within patients of similar histologic classification. To further understand this heterogeneity and thus complexity of lung cancer, investigators have applied various technologies including high throughput analysis of both the genome and proteome. Such approaches have been successful in identifying signatures that may clarify molecular differences in tumors, identify new targets, and improve prognostication. In the last decade, investigators have identified a new mode of gene regulation in the form of noncoding RNAs termed microRNAs (miRNAs or miRs). First determined to be of importance in larval development, microRNAs are approximately 19-22 nucleotide single stranded RNAs that regulate genes by either inducing mRNA degradation or inhibiting translation. MiRNAs have been implicated in several cellular processes including apoptosis, development, proliferation, and differentiation. By regulating hundreds of genes simultaneously, miRNAs have the capacity for regulation of biologic networks. Global alterations in miRNA expression in both solid organ and hematological malignancies suggest their importance in the pathogenesis of disease. To date, both in vivo and in vitro studies in lung cancer demonstrate a dysregulation of miRNA expression. Furthermore, investigators are beginning to identify individual targets and pathways of miRNAs relevant to lung tumorigenesis. Thus, miRNAs may identify critical targets and be important in the pathogenesis of lung cancer. PMID- 19474767 TI - Nargenicin attenuates lipopolysaccharide-induced inflammatory responses in BV-2 cells. AB - Microglia activation has been considered as a major factor associated with neurodegenerative diseases. In this study, we investigated the inhibitory effects of nargenicin, a natural antibiotic from soil bacterium Nocardia, on lipopolysaccharide (LPS)-induced inflammatory activation of microglia. Nargenicin significantly attenuated LPS-induced nitric oxide production in BV-2 microglial cells. Furthermore, nargenicin effectively suppressed the upregulation of interleukin-1beta, tumor necrosis factor alpha, and inducible nitric oxide synthase at both mRNA and protein levels in LPS-stimulated BV-2 microglia. In addition, nargenicin blocked LPS-induced degradation of IkappaB-alpha, indicating that the initial molecular target of nargenicin is the transcription factor nuclear factor-kappaB. These results suggest that nargenicin should be evaluated as a therapeutic agent for inflammatory neurodegenerative diseases. PMID- 19474768 TI - PACAP attenuates 5-HT, histamine, and ATP-evoked Ca2+ transients in astrocytes. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) has neuroprotective properties and plays an important role in neuroinflammation. PACAP38 interacts with its receptors, PAC1, and VPAC, on astrocytes at 10(-8) M to induce biphasic Ca2+ transients, which were reduced to a single transient by the PAC1-blocking PACAP antagonist PACAP6-38. At 10(-12) M even the single transient, corresponding to PAC1 was blocked. PACAP-induced Ca2+ transients were more pronounced in astrocytes cocultured with brain endothelial cells than in monocultured astrocytes, indicating that astrocytes that receive signals from microvessels develop more sensitive signal transduction systems for Ca. In this sensitive system, PACAP38 attenuated 5-HT, histamine, and ATP-evoked Ca2+ transients, showing the anti-inflammatory properties of PACAP. PMID- 19474770 TI - Does P-glycoprotein have a role in the lung clearances of inhaled 99mTc-sestamibi and 99mTc-tetrofosmin? AB - OBJECTIVE: The clearance rate of inhaled 99mTc-sestamibi from the lungs of healthy nonsmoking individuals is much slower than would be expected from its physical properties. The clearance rate is even slower in healthy cigarette smokers. As 99mTc-sestamibi is a substrate for P-glycoprotein (P-gp), pulmonary P gp may be influential in 99mTc-sestamibi clearance and may be upregulated in smokers. 99mTc-tetrofosmin is also a substrate for P-gp, therefore we hypothesized that it would display similar kinetics to 99mTc-sestamibi and support a role for P-gp. We also hypothesized that administration of P-gp modulators would accelerate clearance of 99mTc-sestamibi. METHODS: We measured clearance rates of 99mTc-tetrofosmin in four healthy smokers and four healthy nonsmokers and of 99mTc-sestamibi in six otherwise healthy patients with psoriasis before and after 2 weeks of therapy with cyclosporine A (2.5-5 mg/kg/day) and two healthy women taking the oral contraceptive pill, as both cyclosporine and steroids are known to be P-gp modulators. RESULTS: The clearance rate of 99mTc-tetrofosmin in nonsmokers ranged from 0.38 to 0.63%/min, similar to the previously recorded rate for 99mTc-sestamibi [0.43 (SD 0.083)%/min], but it was not delayed in smokers (range 0.42-0.97%/min). Cyclosporine had no significant effect on 99mTc-sestamibi clearance, although clearance rates in the two women taking the oral contraceptive pill were both fast (0.58 and 0.62%/min). CONCLUSION: Although the role of P-gp expression in the clearance of 99mTc sestamibi remains unproven, we conclude that 99mTc-tetrofosmin is not as P-gp avid as 99mTc-sestamibi. A role for P-gp expression in the clearance of 99mTc sestamibi remains unproven. Higher doses of P-gp inhibitors will be required and clearance rates correlated with immunohistochemical expression of P-gp. PMID- 19474771 TI - Systemic rheumatic disease: a myriad of clinical manifestations. PMID- 19474769 TI - Is the N170 peak of visual event-related brain potentials car-selective? AB - The N170 is a peak of event-related brain potentials commonly acknowledged to be larger in amplitude for face stimuli compared with any other visual object. Recently, the face selectivity of the N170 has been challenged based on the observation of similar N170 amplitude to faces and cars presented full front. Here, we measured the N170 elicited by the same stimulus categories using a one back memory and categorization tasks. We found that N170 mean amplitude was significantly larger for cars than faces at electrode sites considered 'optimal' for measuring N170 face selectivity in the absence of task effects. Furthermore, we found evidence for category selectivity and task dependence in the P1 range. These results support the idea that N170 face selectivity is formally questionable. PMID- 19474772 TI - Sporadic inclusion body myositis: an unsolved mystery. AB - Sporadic inclusion body myositis (sIBM) is considered to be the most common acquired muscle disease associated with aging. It is a disabling disorder still without effective treatment. sIBM causes weakness and atrophy of the distal and proximal muscles. Involvement of quadriceps and deep finger flexors are clues to early diagnosis. Dysphagia in the course of the disease is common. Muscle biopsy shows chronic myopathic features, lymphocytic infiltration invading non-necrotic fibbers, rimmed vacuoles and accumulation of amyloid-related proteins. It remains uncertain whether sIBM is primarily an immune-mediated inflammatory myopathy or a degenerative myopathy with an associated inflammatory component. This review describes the epidemiology and clinical features of the disease as well as the current genetic and pathogenic concepts and therapeutic approaches. Despite recent clues, in many respects sIBM remains an unsolved mystery. PMID- 19474773 TI - [Doppler color echocardiography in the diagnosis of giant cell arteritis]. AB - Although temporal artery biopsy is still the gold standard for the diagnosis of giant cell arteritis (GCA), there is growing evidence that characteristic findings in color Doppler ultrasonography (CD US) of superficial temporal arteries may be of diagnostic relevance. The current question is if CD US can replace biopsy in the diagnosis of temporal artery arteritis. Several studies have been conducted comparing the validity of the American College of Rheumatology criteria (ACR), biopsy and CD US, in the diagnosis of this vasculitis. It has been demonstrated that temporal artery biopsy is the most specific; however it was showed that the sensibility for the biopsy and ACR criteria is not sufficient and that the ACR criteria have a very low positive predictive value, which may have negative implications on the therapeutic approach of the patients. On the other hand, US CD has a better sensibility when compared to the biopsy and the ACR criteria, with a good specificity, positive and negative predictive values. US CD is a cheap, quick and non-invasive test, with a good viability and reliability, as several studies have demonstrated, namely a study held by the authors of this paper. In conclusion, US CD is an effective method in the diagnosis of GCA, especially with a high suspicion index, working also as an auxiliary method in biopsy-guidance, disease activity and recurrence monitoring. PMID- 19474774 TI - [CD4 lymphocytopenia in systemic lupus erythematosus]. AB - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an inflammatory chronic disease characterized by the presence of autoantibodies, immunocomplex production and organ injury. Several alterations of the immune system have been described, namely of CD4 T cells, with particular focus on regulatory subgroup. OBJECTIVE: Quantify peripheral CD4 T cells in a population of patients with SLE and correlate it with lupus activity, affected organs, therapeutics and infections. METHODS: Retrospective study involving all SLE patients seen in the clinical immunology outpatient clinic of the Hospital Geral Santo Antonio, Porto that has done some peripheral blood flow cytometry study. RESULTS: Twenty-nine patients have been evaluated, 16 were taking glucocorticoids and six immunossupressors. The mean SLEDAI at the study time was nine and the ECLAM was three. Thirty-one percent of the patients had leukopenia, 76% lymphocytopenia and the same number CD4 depletion. Fifty-five percent of the patients had CD4 levels lower than 500/mm3, 31% lower than 200/mm3. All patients with SLEDAI > or = 20 and ECLAM > or = 4 had CD4 counts inferior to 500/mm3 and all patients with inactive disease had CD4 superior to 500/mm3. There have been three opportunistic infections: cryptococcal meningitis, pulmonary aspergilosis, Pneumocystis jirovecii pneumonia, all in patients with CD4 counts lower than 500/mm3. CONCLUSION: Decreased CD4 T cells counts have been very common in this study population. There is an inverse relation between CD4 cells counts and disease activity. Opportunistic infections occurred in patients with severe CD4 depletion. PMID- 19474775 TI - Quality of life in systemic lupus erythematosus patients in Northeastern Brazil: Is health-related quality of life a predictor of survival for these patients? AB - OBJECTIVE: To identify social, demographic and clinical characteristics that influence survival of patients with systemic lupus erythematosus (SLE). METHODS: Sixty-three patients with a diagnosis of SLE were studied at our medical services in 1999 and then reviewed in 2005. We utilized a protocol to obtain demographic and clinical traits, activity and damage indices, and health-related quality of life via the SF-36. All statistical tests were performed using a significance level of 5%. RESULTS: Out of the 63 patients examined in 1999, six died, four were lost for the follow-up and the previous protocol was applied to the remaining 53 patients. The six patients who died presented the worst recorded health-related quality of life, in all aspects. The most important observed predictor of death was a mean lower score in the Role-Emotional Domain of the mental health component of the SF-36 (p<0.01). CONCLUSION: Health-related quality of life may be used as possible predictive factor of mortality among patients with SLE. PMID- 19474776 TI - [Applicability of syalometry and other instruments to evaluate xerostomia and xerophtalmia in a Sjogren's Syndrome outpatient clinic]. AB - OBJECTIVES: To evaluate the applicability and utility of unstimulated syalometry and instruments of evaluation of sicca complaints in a Sjogren's syndrome outpatient clinic. MATERIAL AND METHODS: We performed unstimulated syalometry to 45 consecutive Primary Sjogren's Syndrome patients (PSS) and 21 healthy asymptomatic individuals age and sex-matched. PSS patients were further evaluated with Schirmer's test. We applied 3 published questionnaires to PSS patients: Xerostomia Inventory (XI), Oral Health Impact Profile-short form (OHIP) and Ocular Surface Disease Index (OSDI), and correlated the results with syalometry and Schirmer's test. Statistical analysis was performed with SPSS (Mann-Whitney U test and Spearman's correlation). RESULTS: Salivary flux was significantly lower in PSS patients, as compared to controls (0.08+/-0.01 ml/min versus 0.38+/-0.25 ml/min, p=0.000), and decreased with age. Syalometry didn't correlate with Schirmer's test. OHIP scores (mean 26.8 points, ranging from 2 to 43 for a maximum of 56 points) didn't correlate with syalometry neither with Schirmer's test, but showed an association with the XI (p<0.0005) and OSDI (p<0.0005) tests. The XI questionnaire (mean 28.4 points, ranging from 11 to 41 for a maximum of 44 points) correlated with syalometry (p=0.018), with the OHIP questionary (p<0.0005) and with the OSDI scale (p=0.004), although it didn't correlate with Schirmer's test. OSDI scores (mean 56.5 points, ranging from 7 to 90 for a maximum of 100 points) didn't correlate with Schirmer's test neither with syalometry, but associated with the XI (p=0.004) and OHIP (p<0.0005) scales. CONCLUSIONS: Unstimulated syalometry is useful in the evaluation of patients suspected of suffering from Sjogren's syndrome, since it can confirm salivary hypofunction in a quick and cheap manner, allowing to differentiate between healthy individuals and patients. In a specialized clinic, the immediate availability of a salivary functional test is important in the classification of PSS or sicca syndrome. The xerostomia and xerophtalmia impact scales were mutually concordant, and since they evaluate the effects of the disease through time, could be helpful in our daily consultation. PMID- 19474777 TI - Nailfold capillaroscopy abnormalities correlate with cutaneous and visceral involvement in systemic sclerosis patients. AB - OBJECTIVE: The aim of this study was to correlate quantitative and semiquantitative nailfold capillaroscopy (NFC) parameters with the extent of cutaneous and visceral involvement in systemic sclerosis (SSc) patients. METHODS: The presence of clinical and serological alterations was evaluated retrospectively and correlated with NFC findings (number of capillary loops/mm, vascular deletion score and number of enlarged and giant capillary loops). For evaluation of disease extension five manifestations were analyzed: finger pad lesions, skin involvement, esophageal involvement, interstitial lung disease, and pulmonary hypertension. RESULTS: There were 105 NFC examinations in 92 patients, 13 of whom were evaluated at two different time points. Patients with diffuse cutaneous SSc had a higher vascular deletion score than patients with limited cutaneous SSc, sine scleroderma SSc, and overlap syndrome (1.67+/-0.91 vs 0.99+/ 0.82; p=0.0005). Modified Rodnan's skin score correlated positively with capillary deletion, evaluated by the vascular deletion score and the number of capillary loops/mm (p<0.001 and p=0.012; respectively). Patients with three or more involved tracts presented lower number of capillary loops/mm (8.00+/-1.69 vs 9.23+/-1.31 capillary loops/mm; p=0.025) and a higher vascular deletion score (1.41+/-0.95 vs 0.73+/-0.76; p=0.027) when compared to patients with less than three affected tracts. Vascular deletion score was significantly higher in patients with anti-Scl-70 antibodies that in patients without anti-Scl-70 antibodies (p=0.02). CONCLUSIONS: NFC abnormalities correlated positively with the diffuse form of SSc, the degree of cutaneous involvement, the number of affected tracts, and the presence of anti-Scl-70 antibodies. PMID- 19474778 TI - Clinical aspects of Behcet's syndrome in Brazil: a review of 16 cases. AB - OBJECTIVES: The aim of this study was to describe the clinical characteristics of a series of patients with Behcet's syndrome (BS) seen at a referral centre for connective tissue diseases in Bahia, Brazil. MATERIALS AND METHODS: All the patients diagnosed as having BS by the criteria of the International Study Group for Behcet's Disease followed up by the Rheumatology Service of the Hospital Santa Izabel in the year 2007 were included in the study, and were submitted to a clinical evaluation. RESULTS: Sixteen patients were studied, with an equal distribution between genders. Their ages ranged between 19 and 58 years (mean 35.6 +/- 12.9 years). The mean age at disease onset was 27.8 +/- 12.4 years. The clinical manifestations observed include oral ulcers in all cases, cutaneous lesions and articular involvement in 81.3% and genital ulcers in 75% of the patients. Regarding the cutaneous lesions, there were predominantly acneiform lesions (75%) and erythema nodosum (37.5%). Neurological features, including headache, were seen in 37.5% of the patients, and there were 68.8% of ophthalmologic manifestations. Vestibulocochlear symptoms were found in 50% with predominance of vertigo and hypoacusia. Superficial thrombophlebitis and deep venous thrombosis (12.5%) were the most frequent vascular manifestations. All the patients were treated with corticosteroids and/or immunosuppressant agents. CONCLUSIONS: In the present series, it was observed that the spectrum of clinical manifestations of the disease did not differ from series arising in other countries. PMID- 19474779 TI - [Intersticial lung disease as the sole manifestation of antisynthetase syndrome]. AB - The authors report a clinical case of a woman who had a 3 years diagnosis of hipersensitivity pneumonitis based on intersticial lung disease without other manifestations. The diagnosis of antisynthetase syndrome was made three years after the initial symptoms upon the onset of systemic manifestations with articular involvement, myositis and determination of anti-PL 7 antibodies. In this syndrome, the isolated pulmonary involvement is rare. PMID- 19474780 TI - [Primary Sjogren syndrome and inclusion body myositis]. AB - The authors report the case of a 69-years-old woman with Sjogren's syndrome. After 8 years of disease she developed muscle weakness and the diagnosis of inclusion body myositis was established. This is a rare association. The patient had a good response to the immunosupressive treatment. Similar cases can be found in the literature and there seems to be a subset of inclusion body myositis associated with autoimmune diseases that shows a better response to treatment and a more favourable prognosis. PMID- 19474781 TI - [Report of an amyopathic dermatomyositis clinical case]. AB - The authors report a clinical case of a 41-years-old man with astenia and myalgias maintained for many years without an accurate diagnosis. Amyopathic dermatomyositis was diagnosed based on the presence of typical cutaneous lesions and the absence of myositis. Subsequent evidence of subclinical myositis allowed the diagnosis of hypomyophatic dermatomyositis. Finally, the diagnosis of classical dermatomyositis could be made when the patient presented elevated levels of muscle enzimes. There was a good clinical response to imunossupressor therapy and the patient remains asymptomatic. Differences in the clinical management of amyopathic, hypomyopathic and classic dermatomyositis are discussed. PMID- 19474782 TI - [Mutilans psoriatic arthritis]. AB - Mutilans arthritis is a rare psoriatic arthritis subtype. The authors present 2 cases of psoriatic mutilans arthritis, who pictures of the hands and feet and their radiographies are very representative of a severe, disfigurant and disability disease. PMID- 19474783 TI - The value, qualification, and regulatory use of surrogate end points in drug development. AB - The acceptance and use of either surrogate end points (SEPs) or efficient clinical end points are associated with greater and more rapid availability of new medicines as compared with disease situations for which clinical end points are inefficient or no surrogates exist. This review of the history of the development, qualification, and acceptance of key SEPs shows that both successes and failures had three key characteristics: (i) apparent biologic plausibility, (ii) prognostic value for the outcome of the disease, and (iii) an association between changes in the SEP and changes in outcome with therapeutic intervention- the three factors recommended for SEPs in the International Conference on Harmonisation's "Statistical Principles for Clinical Trials." We recommend that only prognostic value be an absolute prerequisite for surrogacy, because therapeutic interventions may not exist a priori, and biological plausibility can be subjective. Ideally, all three of these factors would be traded off against one another in a consistent and transparent risk-management process. PMID- 19474784 TI - QT as a safety biomarker in drug development. AB - The cardiovascular safety of new drugs is an overarching concern for all stakeholders: the pharmaceutical industry and the US Food and Drug Administration (FDA) prior to approval and doctors and patients during postrelease drug use. Of the many cardiac safety concerns that accompany development of new drugs- including those related to vasculature and valvular tissue, the potential for myopathies, and the possibility of other electrophysiologic perturbations--the most pressing concern is the potential for ventricular arrhythmias causing sudden death. PMID- 19474785 TI - A population pharmacokinetic and pharmacodynamic evaluation of pralatrexate in patients with relapsed or refractory non-Hodgkin's or Hodgkin's lymphoma. AB - In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration-time curve (AUC)) could be controlled with body size (e.g., weight or body surface area)-based dosing and that pretreatment with folic acid and vitamin B(12) might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B(12) administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B(12) pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications. PMID- 19474786 TI - The relationships of ABCB1 3435C>T and CYP2B6 516G>T with high-density lipoprotein cholesterol in HIV-infected patients receiving Efavirenz. AB - Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with a favorable increase in high-density lipoprotein cholesterol (HDL-c) level. Isolated studies have found a direct correlation between efavirenz (EFV) exposure and HDL-c level changes. Here we explore the impact that drug disposition variants associated with EFV exposure have on changes in HDL-c level. Seventy-six patients on first-line EFV-based regimens were genotyped for CYP2B6 516G>T and ABCB1 3435C>T. There was a 37% increase (+0.32 mmol/l, P < 0.001) in mean HDL-c level over 48 weeks, and this was univariately associated with gender (male +0.26 mmol/l, female +0.55 mmol/l; P = 0.03), ABCB1 3435C>T (CC +0.26 mmol/l, CT +0.16 mmol/l, TT +0.54 mmol/l; P(ANOVA) = 0.003) and CYP2B6 516 G>T (GG +0.27 mmol/l, GT +0.29 mmol/l, TT +0.72 mmol/l; P(ANOVA) = 0.08). There was a significant association between the cumulative number of predictive genotypes (CYP2B6 516TT or ABCB1 3435TT) and mean HDL-c level change: (group 0 +0.20 mmol/l, group 1 +0.47 mmol/l, group 2 +1.00 mmol/l; P(ANOVA) < 0.0001). These findings need to be validated in independent cohorts. PMID- 19474787 TI - ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. AB - The ABCG2 c.421C>A single-nucleotide polymorphism (SNP) was determined in 660 healthy Finnish volunteers, of whom 32 participated in a pharmacokinetic crossover study involving the administration of 20 mg atorvastatin and rosuvastatin. The frequency of the c.421A variant allele was 9.5% (95% confidence interval 8.1-11.3%). Subjects with the c.421AA genotype (n = 4) had a 72% larger mean area under the plasma atorvastatin concentration-time curve from time 0 to infinity (AUC(0-infinity)) than individuals with the c.421CC genotype had (n = 16; P = 0.049). In participants with the c.421AA genotype, the rosuvastatin AUC(0 infinity) was 100% greater than in those with c.421CA (n = 12) and 144% greater than in those with the c.421CC genotype. Also, those with the c.421AA genotype showed peak plasma rosuvastatin concentrations 108% higher than those in the c.421CA genotype group and 131% higher than those in the c.421CC genotype group (P < or = 0.01). In MDCKII-ABCG2 cells, atorvastatin transport was increased in the apical direction as compared with vector control cells (transport ratio 1.9 +/- 0.1 vs. 1.1 +/- 0.1). These results indicate that the ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and, even more so, of rosuvastatin-potentially affecting the efficacy and toxicity of statin therapy. PMID- 19474788 TI - Structural insight into the autoinhibition mechanism of AMP-activated protein kinase. AB - The AMP-activated protein kinase (AMPK) is characterized by its ability to bind to AMP, which enables it to adjust enzymatic activity by sensing the cellular energy status and maintain the balance between ATP production and consumption in eukaryotic cells. It also has important roles in the regulation of cell growth and proliferation, and in the establishment and maintenance of cell polarity. These important functions have rendered AMPK an important drug target for obesity, type 2 diabetes and cancer treatments. However, the regulatory mechanism of AMPK activity by AMP binding remains unsolved. Here we report the crystal structures of an unphosphorylated fragment of the AMPK alpha-subunit (KD-AID) from Schizosaccharomyces pombe that contains both the catalytic kinase domain and an autoinhibitory domain (AID), and of a phosphorylated kinase domain from Saccharomyces cerevisiae (Snf1-pKD). The AID binds, from the 'backside', to the hinge region of its kinase domain, forming contacts with both amino-terminal and carboxy-terminal lobes. Structural analyses indicate that AID binding might constrain the mobility of helix alphaC, hence resulting in an autoinhibited KD AID with much lower kinase activity than that of the kinase domain alone. AMP activates AMPK both allosterically and by inhibiting dephosphorylation. Further in vitro kinetic studies demonstrate that disruption of the KD-AID interface reverses the autoinhibition and these AMPK heterotrimeric mutants no longer respond to the change in AMP concentration. The structural and biochemical data have shown the primary mechanism of AMPK autoinhibition and suggest a conformational switch model for AMPK activation by AMP. PMID- 19474789 TI - A spatial gradient coordinates cell size and mitotic entry in fission yeast. AB - Many eukaryotic cell types undergo size-dependent cell cycle transitions controlled by the ubiquitous cyclin-dependent kinase Cdk1 (refs 1-4). The proteins that control Cdk1 activity are well described but their links with mechanisms monitoring cell size remain elusive. In the fission yeast Schizosaccharomyces pombe, cells enter mitosis and divide at a defined and reproducible size owing to the regulated activity of Cdk1 (refs 2, 3). Here we show that the cell polarity protein kinase Pom1, which localizes to cell ends, regulates a signalling network that contributes to the control of mitotic entry. This network is located at cortical nodes in the middle of interphase cells, and these nodes contain the Cdk1 inhibitor Wee1, the Wee1-inhibitory kinases Cdr1 (also known as Nim1) and Cdr2, and the anillin-like protein Mid1. Cdr2 establishes the hierarchical localization of other proteins in the nodes, and receives negative regulatory signals from Pom1. Pom1 forms a polar gradient extending from the cell ends towards the cell middle and acts as a dose-dependent inhibitor of mitotic entry, working through the Cdr2 pathway. As cells elongate, Pom1 levels decrease at the cell middle, leading to mitotic entry. We propose that the Pom1 polar gradient and the medial cortical nodes generate information about cell size and coordinate this with mitotic entry by regulating Cdk1 through Pom1, Cdr2, Cdr1 and Wee1. PMID- 19474790 TI - Dual nature of the adaptive immune system in lampreys. AB - Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here we show that in sea lampreys (Petromyzon marinus) VLRA and VLRB anticipatory receptors are expressed by separate lymphocyte populations by monoallelic VLRA or VLRB assembly, together with expression of cytosine deaminase 1 (CDA1) or 2 (CDA2), respectively. Distinctive gene expression profiles for VLRA(+) and VLRB(+) lymphocytes resemble those of mammalian T and B cells. Although both the VLRA and the VLRB cells proliferate in response to antigenic stimulation, only the VLRB lymphocytes bind native antigens and differentiate into VLR antibody-secreting cells. Conversely, VLRA lymphocytes respond preferentially to a classical T-cell mitogen and upregulate the expression of the pro-inflammatory cytokine genes interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF). The finding of T-like and B-like lymphocytes in lampreys offers new insight into the evolution of adaptive immunity. PMID- 19474791 TI - Adaptation and the evolution of parasite virulence in a connected world. AB - Adaptation is conventionally regarded as occurring at the level of the individual organism, where it functions to maximize the individual's inclusive fitness. However, it has recently been argued that empirical studies on the evolution of parasite virulence in spatial populations show otherwise. In particular, it has been claimed that the evolution of lower virulence in response to limited parasite dispersal provides proof of Wynne-Edwards's idea of adaptation at the group level. Although previous theoretical work has shown that limited dispersal can favour lower virulence, it has not clarified why, with five different suggestions having been given. Here we show that the effect of dispersal on parasite virulence can be understood entirely within the framework of inclusive fitness theory. Limited parasite dispersal favours lower parasite growth rates and, hence, reduced virulence because it (1) decreases the direct benefit of producing offspring (dispersers are worth more than non-dispersers, because they can go to patches with no or fewer parasites), and (2) increases the competition for hosts experienced by both the focal individual ('self-shading') and their relatives ('kin shading'). This demonstrates that reduced virulence can be understood as an individual-level adaptation by the parasite to maximize its inclusive fitness, and clarifies the links with virulence theory more generally. PMID- 19474793 TI - Bio-art: the ethics behind the aesthetics. AB - Bio-art represents a crossover of art and the biological sciences, with living matter, such as genes, cells or animals, as its new media. Such manipulations of life require collaborations with scientists and considerable financial backing. Herein, I consider bio-art that goes 'under the skin' - in which DNA, cells or proteins are used as the media and means - to highlight the ethical implications of reducing life to art. PMID- 19474792 TI - Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle. AB - Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phosphatase. However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces pombe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends. We discovered that Pom1 is also a dose-dependent G2-M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family. This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. Whereas Cdr1 and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdr1 and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M phase entry. PMID- 19474795 TI - Midodrine for the treatment of organic anejaculation but not spinal cord injury: a prospective randomized placebo-controlled double-blind clinical study. AB - Anejaculation is a rare cause of infertility and adversely affects the general sense of well-being and perception of sexual life satisfaction. Evidence to support effective and noninvasive treatment for this ejaculatory disorder is lacking. This study aimed to evaluate the efficacy and safety of midodrine (alpha(1)-adrenergic receptor agonist) for the treatment of organic anejaculation but not spinal cord injury (SCI). A total of 128 patients were randomly assigned to oral midodrine 7.5-15 mg per day in a stepwise approach (group 1, n=64), or a similar regimen of placebo (group 2, n=64). They underwent a complete physical examination, echocardiography, 12-lead electrocardiogram, transrectal ultrasonography, complete blood count and blood chemistry. Hormonal assays included serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin and testosterone. To rule out other sexual dysfunction, patients also completed the International Index of Erectile Function questionnaire. Psychiatric disorders were excluded by appropriate tests. Outcome measure was reversal of the anejaculation. None of the patients in the placebo group achieved antegrade or retrograde ejaculation. At the end of study, antegrade, retrograde and antegrade+retrograde ejaculation occurred in 18 (29.5%), 8 (13.1%) and 9 (14.8%) patients in midodrine group, respectively (all P=0.01). The most and least favorable responses were among patients with multiple sclerosis and bilateral sympathectomy, respectively. Midodrine improved ejaculation function in a dose dependent manner. Four participants (6.3%) in midodrine group discontinued this study for reasons of adverse events. In patients with organic anejaculation but without SCI midodrine can reverse anejaculation in more than 50% of patients. Further studies are needed, however, for the evaluation of different treatment regimens in anejaculation therapy. PMID- 19474794 TI - An additional role for SUMO in ubiquitin-mediated proteolysis. AB - Although the post-translational modification of proteins with small ubiquitin like modifier (SUMO) has a role in many biological processes, it was thought that SUMO, unlike ubiquitin, does not target proteins for degradation. However, these views need to be revised, as recent findings in yeast and human cells indicate that SUMO can act as a signal for the recruitment of E3 ubiquitin ligases, which leads to the ubiquitylation and degradation of the modified protein. PMID- 19474796 TI - Effects of vardenafil administration on intravaginal ejaculatory latency time in men with lifelong premature ejaculation. AB - Premature ejaculation (PE) is thought to be the most common male sexual dysfunction; however, the prevalence of lifelong (LL)-PE is relatively low. The aim of this study was to investigate the effects of on-demand vardenafil (10 mg) to modify the intravaginal ejaculatory latency time (IELT) in men with LL-PE without erectile dysfunction. Forty-two men (18-35 years) were enrolled in a 16 week, double-blind, placebo-controlled, cross-over study. Primary end point was the modification from baseline of IELT assessed by stopwatch technique; secondary end points were post-ejaculatory refractory time (PERT) and variations of scores at the Index of Premature Ejaculation questionnaire. The changes in geometric mean IELT were superior after taking vardenafil (0.6+/-0.3 vs 4.5+/-1.1 min, P<0.01), compared with placebo (0.7+/-0.3 vs 0.9+/-1.0 min, ns). PERT dropped significantly after vardenafil (16.7+/-2.0 vs 4.3+/-0.9 min, P<0.001), compared with placebo (15.3+/-2.2 vs 15.8+/-2.3 min). Patients who took vardenafil (vs placebo) reported significantly (P<0.01) increased ejaculatory control (6+/-2 vs 16+/-2), improved overall sexual satisfaction (7+/-2 vs 15+/-1) and distress (4+/ 1 vs 8+/-1) scores, respectively. Multiple regression analysis (r(2)=0.86) for IELT by the number of attempts at sexual intercourse showed significant differences between the slopes of lines for placebo and vardenafil (P<0.0001). The most common adverse events for vardenafil (vs placebo) were headache (10 vs 3%), flushing (12 vs 0%) and dyspepsia (10 vs 0%), which tended to disappear over the time. In conclusion, in our study, vardenafil increased IELT and reduced PERT in men with LL-PE. Besides, improvements in confidence, perception of ejaculatory control and overall sexual satisfaction were reported. PMID- 19474797 TI - Fetal bone strength and umbilical cord length. AB - OBJECTIVE: Activity has been demonstrated in promoting bone mass in infants and adults. One of the major signs of fetal activity may be the length of the umbilical cord. We hypothesized that the fetus with a shortened umbilical cord may have low bone mineralization because of decreased movement or activity. STUDY DESIGN: We investigated eight healthy term infants with shortened umbilical cords and 15 control term infants. Mothers with pre-eclampsia or hypertension, chorioamnionitis or prolonged ruptured of membranes were excluded from the study. Mother's age, parity, infants' gender, and birth and placenta weights were recorded. The umbilical cord length and diameter were measured as well as the newborn's tibial speed of sound (SOS). SOS measurements (Sunlight Omnisense 7000P instrument) were obtained at the tibial midshaft. RESULTS: Measurement reproducibility was 0.8+/-0.6% (mean+/-s.d.) for repeat SOS measures. There were no differences between the two groups in mother's age (24.6+/-5.8 vs 25.8+/-3.3 years), parity (2+/-1 vs 2+/-1), infant's gender (25% females vs 47% females), birth weights (3320+/-451 vs 3409+/-452 g), or placental weights (521+/-69 vs 588+/-105 g). Umbilical cord diameters were also similar, 1.1+/-0.3 vs 1.1+/-0.2 cm. However, there was a difference in the cord length between the two groups, 46+/-2 vs 57+/-4 cm (Mann-Whitney, P<0.001). The newborn infants with the shorter umbilical cord also had lower tibial SOS compared with controls, 3047+/-107 vs 3194+/-311 m/sec (Mann-Whitney, P<0.05). Tibial SOS was related to the infant's umbilical cord length (r=0.57, P<0.01) but not to infant's birth weight, gender, umbilical cord diameter, maternal age, or placenta weight. CONCLUSION: Infants with a short umbilical cord length have lower bone strength. PMID- 19474798 TI - Residual cardiovascular risk in treated hypertension and hyperlipidaemia: the PRIME Study. AB - Although pharmacological treatments of hypertension and dyslipidaemia are both associated with a reduction in cardiovascular risk, little is known about the degree of cardiovascular risk remaining in treated individuals, by assessing the levels of their risk factors achieved, that is their 'residual cardiovascular risk'. We then used the data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME), which involved 9649 men aged 50-59 years, from France and Northern Ireland with a 10-year follow-up, to test the presence of specific residual cardiovascular risks of coronary heart disease, stroke, total of fatal and non-fatal cardiovascular events and cardiovascular mortality, in patients treated with antihypertensive agents or lipid-lowering agents. In the whole cohort, a total of 796 patients developed a fatal or non-fatal cardiovascular event. Antihypertensive drug use at baseline was significantly associated (RR=1.50, 95% CI: 1.25-1.80) with total cardiovascular event risk, but not lipid-lowering drug use, after adjusting for classic risk factors (age, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure and diabetes). Similar results were obtained for coronary heart disease (RR=1.46, 95% CI: 1.18-1.80), stroke (RR=1.75, 95% CI: 1.14-2.70) and cardiovascular death (RR=1.62, 95% CI: 1.02-2.58), but neither for total death (RR=1.15, 95% CI: 0.89-1.48) nor for non-cardiovascular death (RR=1.00, 95% CI: 0.74-1.36). For any cardiovascular end point, residual risks did not globally differ according to the antihypertensive drug class prescribed at baseline. In conclusion, treatment with antihypertensive agents, but not with lipid-lowering agents, was associated with a sizeable residual cardiovascular risk, suggesting that more efficient risk reduction strategies in hypertension should be developed as a priority. PMID- 19474799 TI - Identification of MNDA as a new marker for nodal marginal zone lymphoma. AB - Clinical and biological studies on nodal marginal zone lymphoma (NMZL) are hampered by the lack of specific diagnostic markers and the low reproducibility of this diagnosis. A comparative expression-profiling study has shown a set of markers to be differentially expressed in NMZL compared with follicular lymphoma (FL), including myeloid cell nuclear differentiation antigen (MNDA), a nuclear protein expressed by myeloid cells and a subset of B-cells. The aim of this study was to characterize the expression of MNDA in normal and reactive human tissue, and in a large series of non-Hodgkin's B-cell lymphomas, with particular emphasis on NMZL and FL. Our results showed that MNDA is expressed in normal tissue by a subset of the marginal zone B cells. They also showed MNDA expression in subgroups of chronic lymphocytic leukemia, mantle-cell lymphoma, and diffuse large B-cell lymphoma, but MNDA was especially expressed by lymphomas derived from the marginal zone, such as mucosa-associated lymphoid-tissue lymphoma, splenic marginal-zone lymphoma and NMZL. MNDA expression was rarely observed in FL, a characteristic that is of potential value in distinguishing between NMZL and FL. MNDA expression is thus a useful tool for the recognition of NMZL. PMID- 19474800 TI - Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. AB - Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML), offering patients several targeted therapeutic options that provide the possibility of sustained remissions and prolonged survival. With the availability of imatinib, nilotinib and dasatinib, physicians must weigh the efficacy and safety profile of each agent when choosing the best therapeutic option for individual patients. Each agent targets tyrosine kinases within the cell uniquely to cause the desired antiproliferative effect. In addition to inhibiting the BCR-ABL kinase, imatinib and nilotinib target the same array of other tyrosine kinases, including c-KIT and platelet-derived growth factor receptor (PDGFR), albeit with differing potencies. While targeting BCR-ABL with the highest potency among approved agents in CML, dasatinib also targets a broad array of off-target kinases, including SRC family members, PDGFR and EPHB4. The differences in kinase inhibition profiles among these agents in vitro probably account for the differing clinical safety profiles of these agents. This paper reviews the various kinases inhibited by imatinib, nilotinib and dasatinib, and describes the potential impact of kinase inhibition on the efficacy and safety of each agent. PMID- 19474801 TI - Cytogenetic profile of de novo acute myeloid leukemia: a study based on 1432 patients in a single institution of China. AB - Geographic heterogeneity of cytogenetic patterns in hematological malignancies has been reported earlier, but few systematic studies of cytogenetic abnormalities in acute myeloid leukemia (AML) patients are available. We examined the karyotypic patterns in 1432 de novo AML patients from a single center in China and compared our data with reports from other regions of the world. Chromosomal abnormalities were detected in 746 (58%) cases. The most frequent cytogenetic abnormality was t(15;17), detected in 14% of successful cases, followed by t(8;21) in 8%, and t(9;22), +21 and +8 each in 2%. The mean age of patients with a translocation karyotype was significantly younger than that of patients with normal, deletion or trisomy karyotypes. A higher incidence of AML M3 and a lower frequency of M4 were observed in the Asian population and the frequencies of certain cytogenetic aberrations were different from those in the earlier reports. Population-based age-specific incidences of AML were calculated and compared with those in western reports. PMID- 19474802 TI - cis-Urocanic acid stimulates primary human keratinocytes independently of serotonin or platelet-activating factor receptors. AB - Urocanic acid (UCA) is a major epidermal chromophore that undergoes trans to cis isomerization after ultraviolet radiation (UVR). cis-UCA suppresses cell-mediated immunity. Recent studies suggest that cis-UCA binds to serotonin (5 hydroxytryptamine) 2A (5-HT(2A)) receptor and that antagonists of 5-HT(2A) and the platelet-activating factor (PAF) receptor can block cis-UCA-induced immune suppression in mice. Here, we examined the involvement of 5-HT(2A) and PAF receptors in the ability of cis-UCA to stimulate immunomodulatory mediator production in primary human keratinocytes. Using real-time reverse transcription PCR (RT-PCR), PAF but not 5-HT(2A) receptor mRNA was constitutively expressed in primary human keratinocytes. Treatment with cis-UCA increased prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), and IL-6 secretion, whereas 5 HT only stimulated IL-6 production. Pretreatment with a 5-HT receptor antagonist partially inhibited IL-6 increase by 5-HT, but did not inhibit mediator production by cis-UCA. Similarly, a PAF receptor antagonist did not inhibit cis UCA-induced increase in PGE(2). Intracellular calcium mobilization studies using a human epithelial cell line stably transfected with PAF receptor also showed little evidence that cis-UCA stimulated PAF receptor and it did not bind to this receptor. Thus, cis-UCA stimulates mediator production by a pathway that is independent of these receptors in human keratinocytes, and these cells may not be the major target for cis-UCA-induced immune suppression. PMID- 19474803 TI - Interdependence between heme oxygenase-1 induction and estrogen-receptor-beta signaling mediates photoimmune protection by UVA radiation in mice. AB - Previous studies have found that signaling by the estrogen receptor-beta (Er beta) attenuated solar-simulated UV radiation (SSUV)-induced immunosuppression. This study seeks evidence for a common mechanism for this immunoprotection for both Er-beta signaling and irradiation with the UVA waveband. In Skh:hr-1 hairless mice, the immunoprotection afforded by UVA exposure against subsequent UVB or cis-urocanic acid suppression of contact hypersensitivity (CHS) was abrogated by treatment with the antiestrogen, ICI 182,780. Furthermore, in normal C57BL mice, UVA enrichment of UVA/UVB sources provided protection against UVB suppressed CHS and upregulated epidermal IL-10 expression, but this protection was inhibited in Er-beta-/- mice. These observations indicated that the immunoprotective response to UVA was dependent on Er-beta signaling. As earlier studies have established that UVA photoimmune protection depends on the induction of the stress enzyme, heme oxygenase (HO)-1, its activity was examined relative to Er-beta. Immunoprotection against SSUV by 17-beta-estradiol was prevented by inhibiting HO enzyme activity; immunoprotection against cis-urocanic acid by carbon monoxide (HO product) was prevented by ICI 182,780. In addition, the HO-1 gene was unresponsive to UVA induction in Er-beta-/- mice. Therefore, HO-1 inducibility and Er-beta signaling are interdependent requisite responses to the UVA waveband for its immunoprotective action against UVB exposure. PMID- 19474804 TI - Chemokine receptors in T-cell-mediated diseases of the skin. AB - The chemokine/chemokine receptor network is an integral element of the complex system of homeostasis and immunosurveillance. Initially studied because of their role in coordinating tissue-specific migration and activation of leucocytes, chemokines have been implicated in the pathogenesis of various malignancies and diseases with strong inflammatory components. We discuss recent findings suggesting a critical involvement of chemokine receptor interactions in the immunopathogenesis of classical inflammatory skin disorders such as psoriasis and atopic dermatitis, as well as neoplastic diseases with a T-cell origin, such as mycosis fungoides. A deeper understanding of the underlying contribution of the chemokine network in the disease processes is key for the development of selective targeted immunotherapeutics that may meet the delicate balance between efficacy and safety. PMID- 19474805 TI - Recessive epidermolytic hyperkeratosis caused by a previously unreported termination codon mutation in the keratin 10 gene. PMID- 19474807 TI - A muscle-targeting peptide displayed on AAV2 improves muscle tropism on systemic delivery. AB - Adeno-associated virus (AAV) has become a leading gene transfer vector for striated muscles. However, the AAV vectors also exhibit broad tropisms after systemic delivery. In an attempt to improve muscle tropism, we inserted a 7-amino acid (ASSLNIA) muscle-targeting peptide (MTP) in the capsids of AAV2 at residue 587 or 588, generating AAV(587)MTP and AAV(588)MTP. In vitro studies showed that both viruses diminished their infectivity on non-muscle cell lines as well as on un-differentiated myoblasts; however, preserved or enhanced their infectivity on differentiated myotubes. AAV(587)MTP, but not AAV(588)MTP, also abolished its heparin-binding capacity and infected myotubes in a heparin-independent manner. Furthermore, in vivo studies by intravenous vector administration in mice showed that AAV(587)MTP enhanced its tropism to various muscles and particularly to the heart (24.3-fold of unmodified AAV2), whereas reduced its tropism to the non muscle tissues such as the liver, lungs, spleen and so on. This alteration of tissue tropism is not simply because of the loss of heparin-binding, as a mutant AAV2 (AAVHBSMut) containing heparin-binding site mutations lost infectivity on both non-muscle and muscle cells. Furthermore, free MTP peptide, but not the scrambled control peptide, competitively inhibited AAV(587)MTP infection on myotubes. These results suggest that AAV2 could be re-targeted to the striated muscles by a MTP inserted after residue 587 of the capsids. This proof of principle study showed first evidence of peptide-directed muscle targeting on systemic administration of AAV vectors. PMID- 19474808 TI - Adenovirus-mediated gene transfer of fibromodulin inhibits neointimal hyperplasia in an organ culture model of human saphenous vein graft disease. AB - Poor long-term graft patency remains a major limitation of coronary artery bypass grafting using saphenous vein aortocoronary grafts. Neointimal hyperplasia (NIH) represents the principal mechanism of graft failure; a substantial body of evidence implicates transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of NIH. The small leucine-rich proteoglycans decorin and fibromodulin possess TGF-beta-antagonist activity to differing extents and with differing avidities for the isoforms of TGF-beta. We compared their ability to inhibit NIH in an ex vivo model of human saphenous vein organ culture following adenovirus-mediated gene transfer. Surgically prepared human saphenous vein segments received adenovirus expressing fibromodulin (Ad5-Fmod), decorin (Ad5 Dcn), beta-galactosidase (Ad5-lacZ) or vehicle-only. Computerized morphometry 14 days after infection revealed significantly reduced neointimal area, neointimal thickness and intima/media ratio in Ad5-Fmod- and Ad5-Dcn-infected veins. Each parameter was significantly smaller in Ad5-Fmod- than in Ad5-Dcn-exposed segments. Fibrillar collagen content and levels of biologically active TGF-beta were lower in vessels receiving Ad5-Fmod or Ad5-Dcn than in those receiving Ad5 lacZ or vehicle-only. Fibromodulin is a more potent inhibitor of NIH in cultured human saphenous vein than decorin and offers potential therapeutic benefits in saphenous vein graft failure (and possibly in other forms of accelerated atherosclerosis) by reduction of associated neointima formation. PMID- 19474806 TI - Systemic delivery of AAV8 in utero results in gene expression in diaphragm and limb muscle: treatment implications for muscle disorders. AB - One of the major challenges in the treatment of primary muscle disorders, which often affect many muscle groups, is achieving efficient, widespread transgene expression in muscle. In utero gene transfer can potentially address this problem by accomplishing the gene delivery when the tissue mass is small and the immune system is immature. Earlier studies with systemic in utero adeno-associated viral (AAV) vector serotype 1 gene delivery to embryonic day 16 (E-16) pups resulted in high levels of transduction in diaphragm and intercostal muscles, but no detectable transgene expression in limb muscles. Recently, newer AAV serotypes, such as AAV8, have shown widespread and high transgene expression in skeletal muscles and diaphragm by systemic delivery in adult and neonatal mice. We tested AAV8 vector gene delivery by intraperitoneal administration in E-16 mice in utero. Using an AAV8 vector carrying a lacZ reporter gene, we observed high-level transduction of diaphragm and intercostal muscles and more moderate transduction of multiple limb muscles and heart. Our current studies show the potential of AAV8 to achieve widespread muscle transduction in utero and suggest its therapeutic potential for primary muscle disorders. PMID- 19474810 TI - PML has a predictive role in tumor cell permissiveness to interferon-sensitive oncolytic viruses. AB - The oncotropic phenotypes of several viruses correlate with tumor-associated deficiencies within interferon (IFN) signaling pathways. This observation formed the conceptual basis for developing oncolytic viruses deleted for viral proteins that inhibit the host IFN-dependent antiviral response, such as herpes simplex virus type-1 infected cell protein-0 (ICP0) and vesicular stomatitis virus matrix protein. Many viruses have evolved means to disrupt promyelocytic leukemia protein (PML) nuclear bodies. For example, ICP0 promotes PML degradation to inhibit the antiviral activities of this IFN-stimulated gene. As PML is downregulated in a variety of tumors, we hypothesized ICP0-null herpes simplex type-1 viruses are selectively oncolytic in tumors with impaired PML expression. We illustrate that ICP0-null herpes simplex type-1 viruses target tumor cells that either possess impaired PML signaling or cannot upregulate PML because of impaired IFN responsiveness. Disruption of PML signaling through overexpression of the dominant-negative protein PML-retinoic acid receptor alpha in PML-positive cells renders them sensitive to oncolysis by ICP0-null herpes simplex virus type 1 and vesicular stomatitis virus M protein mutant viruses, whereas PML overexpression reverses this phenomenon. Together, these data illustrate that PML mediates an antiviral mechanism that predicts the tropism of IFN-sensitive oncolytic viruses. To our knowledge, these viruses are the first examples of anti cancer therapeutics capable of targeting deficiencies in PML expression. PMID- 19474809 TI - Analysis of neuronal proliferation, migration and differentiation in the postnatal brain using equine infectious anemia virus-based lentiviral vectors. AB - Ongoing neurogenesis in discrete sectors of the adult central nervous system depends on the mitotic activity of an elusive population of adult stem cells. The existence of adult neural stem cells provides an alternative approach to transplantation of embryonic stem cells in cell-based therapies. Owing to the limited intrinsic fate of adult stem cells and inhibitory nature of the adult brain for neurogenesis, accommodation for circuit replacement in the brain will require genetic and epigenetic manipulation. Here, we show that a replication incompetent Equine Infectious Anemia Virus (EIAV) is highly suitable for stable and persistent gene transfer to adult neural stem cells. The transduced regions were free of long-lasting neuroimmune responses to EIAV. Transduction in the subventricular zone was specific to the stem cell niche, but spared the progeny of adult neural stem cells that includes transit amplifying progenitors (TAPs) and migrating neuroblasts. With time, EIAV-transduced stem cells passed on the transgene to TAPs and migrating neuroblasts, which ultimately differentiated into neurons in the olfactory bulbs. We show that EIAV is highly suitable for discovery and assessment of mechanisms that regulate proliferation, migration and differentiation in the postnatal brain. PMID- 19474811 TI - siRNA silencing of keratinocyte-specific GFP expression in a transgenic mouse skin model. AB - Small interfering RNAs (siRNAs) can be designed to specifically and potently target and silence a mutant allele, with little or no effect on the corresponding wild-type allele expression, presenting an opportunity for therapeutic intervention. Although several siRNAs have entered clinical trials, the development of siRNA therapeutics as a new drug class will require the development of improved delivery technologies. In this study, a reporter mouse model (transgenic click beetle luciferase/humanized monster green fluorescent protein) was developed to enable the study of siRNA delivery to skin; in this transgenic mouse, green fluorescent protein reporter gene expression is confined to the epidermis. Intradermal injection of siRNAs targeting the reporter gene resulted in marked reduction of green fluorescent protein expression in the localized treatment areas as measured by histology, real-time quantitative polymerase chain reaction and intravital imaging using a dual-axes confocal fluorescence microscope. These results indicate that this transgenic mouse skin model, coupled with in vivo imaging, will be useful for development of efficient and 'patient-friendly' siRNA delivery techniques and should facilitate the translation of siRNA-based therapeutics to the clinic for treatment of skin disorders. PMID- 19474812 TI - Therapeutic silencing of an endogenous gene by siRNA cream in an arthritis model mouse. AB - Recent advances of biotechnology have laid the groundwork for potent and specific molecular-targeting therapies including RNA interference. The largest remaining hurdle for widespread use of this technology in skin is an effective delivery system. Here, we demonstrate an effective topical delivery system using a cream formulation containing a small-interfering RNA (siRNA) that specifically targets osteopontin (OPN). OPN is a validated target in numerous inflammatory diseases, including rheumatoid arthritis (RA). The siRNA targeting OPN was incorporated into a cream formulation GeneCream that penetrates the stratum corneum, depositing siRNA in the epidermis, dermis, and to a lesser extent, subcutaneous tissue. In addition, when the OPN siRNA cream was topically applied to the skin of a collagen antibody-induced RA mouse model, the siRNA cream prevented the occurrence of severe, irreversible damage to bone and cartilage. Thus, the siRNA cream provides effective delivery of active OPN siRNA, suggesting this formulation may represent a platform technology for delivery of siRNAs for treating various disorders including RA. PMID- 19474813 TI - Life without light: microbial diversity and evidence of sulfur- and ammonium based chemolithotrophy in Movile Cave. AB - Microbial diversity in Movile Cave (Romania) was studied using bacterial and archaeal 16S rRNA gene sequence and functional gene analyses, including ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), soxB (sulfate thioesterase/thiohydrolase) and amoA (ammonia monooxygenase). Sulfur oxidizers from both Gammaproteobacteria and Betaproteobacteria were detected in 16S rRNA, soxB and RuBisCO gene libraries. DNA-based stable-isotope probing analyses using 13C-bicarbonate showed that Thiobacillus spp. were most active in assimilating CO2 and also implied that ammonia and nitrite oxidizers were active during incubations. Nitrosomonas spp. were detected in both 16S rRNA and amoA gene libraries from the 'heavy' DNA and sequences related to nitrite-oxidizing bacteria Nitrospira and Candidatus 'Nitrotoga' were also detected in the 'heavy' DNA, which suggests that ammonia/nitrite oxidation may be another major primary production process in this unique ecosystem. A significant number of sequences associated with known methylotrophs from the Betaproteobacteria were obtained, including Methylotenera, Methylophilus and Methylovorus, supporting the view that cycling of one-carbon compounds may be an important process within Movile Cave. Other sequences detected in the bacterial 16S rRNA clone library included Verrucomicrobia, Firmicutes, Bacteroidetes, alphaproteobacterial Rhodobacterales and gammaproteobacterial Xanthomonadales. Archaeal 16S rRNA sequences retrieved were restricted within two groups, namely the Deep-sea Hydrothermal Vent Euryarchaeota group and the Miscellaneous Crenarchaeotic group. No sequences related to known sulfur-oxidizing archaea, ammonia-oxidizing archaea, methanogens or anaerobic methane-oxidizing archaea were detected in this clone library. The results provided molecular biological evidence to support the hypothesis that Movile Cave is driven by chemolithoautotrophy, mainly through sulfur oxidation by sulfur-oxidizing bacteria and reveal that ammonia- and nitrite-oxidizing bacteria may also be major primary producers in Movile Cave. PMID- 19474815 TI - Is it time to stop starving premature infants? PMID- 19474816 TI - Beckwith-Wiedemann syndrome associated with congenital hypothyroidism in a preterm neonate: a case report and literature review. AB - This report describes for the first time the association of Beckwith-Wiedemann syndrome (BWS) and hypothyroidism in a 25 weeks preterm neonate. Antenatal diagnosis of exomphalos in association with postnatal transient hypoglycemia and macroglossia formed the basis of the diagnosis of BWS. Primary hypothyroidism was detected on routine Guthrie card examination. Molecular DNA analysis demonstrated biparental inheritance of chromosome 11p15.5. Dosage analysis of differently methylated region showed evidence of loss of maternal methylation at KvDMR1. PMID- 19474814 TI - Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria. AB - Genomic islands have been shown to harbor functional traits that differentiate ecologically distinct populations of environmental bacteria. A comparative analysis of the complete genome sequences of the marine Actinobacteria Salinispora tropica and Salinispora arenicola reveals that 75% of the species specific genes are located in 21 genomic islands. These islands are enriched in genes associated with secondary metabolite biosynthesis providing evidence that secondary metabolism is linked to functional adaptation. Secondary metabolism accounts for 8.8% and 10.9% of the genes in the S. tropica and S. arenicola genomes, respectively, and represents the major functional category of annotated genes that differentiates the two species. Genomic islands harbor all 25 of the species-specific biosynthetic pathways, the majority of which occur in S. arenicola and may contribute to the cosmopolitan distribution of this species. Genome evolution is dominated by gene duplication and acquisition, which in the case of secondary metabolism provide immediate opportunities for the production of new bioactive products. Evidence that secondary metabolic pathways are exchanged horizontally, coupled with earlier evidence for fixation among globally distributed populations, supports a functional role and suggests that the acquisition of natural product biosynthetic gene clusters represents a previously unrecognized force driving bacterial diversification. Species-specific differences observed in clustered regularly interspaced short palindromic repeat sequences suggest that S. arenicola may possess a higher level of phage immunity, whereas a highly duplicated family of polymorphic membrane proteins provides evidence for a new mechanism of marine adaptation in Gram-positive bacteria. PMID- 19474817 TI - Use of CT angiography in the diagnosis of total anomalous venous return. AB - Total anomalous pulmonary venous return (TAPVR) is an uncommon cause of cyanotic congenital heart disease in the neonatal period. This diagnosis is often made by echocardiography. We present two cases where echocardiography was not confirmatory. Computerized tomography (CT) scan of the chest and abdomen with contrast was performed instead of cardiac catheterization to establish the diagnosis. We suggest that CT with contrast is a noninvasive modality to obtain anatomic details of pulmonary venous drainage in TAPVR when echocardiography is inconclusive. PMID- 19474818 TI - Chest wall mesenchymal hamartoma. PMID- 19474820 TI - Innocent white blood cells in sporadic Creutzfeldt-Jakob disease? PMID- 19474822 TI - Putting clinical trials on trial. PMID- 19474823 TI - Mineral metabolism: Should cinacalcet be used in patients who are not on dialysis? AB - Cinacalcet is an effective treatment for secondary hyperparathyroidism in patients on dialysis. Until now, no randomized, placebo-controlled, long-term trial has tested this drug in individuals with chronic kidney disease who are not receiving dialysis. PMID- 19474824 TI - Transplantation: Tackling inactivity on the waiting list for transplantation. AB - An analysis of the US kidney transplant waiting list suggests that recording a potential recipient as 'inactive', during which time he or she cannot be offered a donor organ, is becoming increasingly common and is not in patients' best interests. PMID- 19474825 TI - Pediatric nephrology: Estimating GFR in children: Schwartz redux. AB - one of the early products of the Chronic Kidney Disease in Children (CKiD) study has been an updated equation for estimating GFR in children on the basis of demographic and laboratory parameters. This formula is comparable in form and performance to the MDRD equations for adults in clinical trials first published a decade ago. PMID- 19474826 TI - Polycystic kidney disease: The cadence of kidney growth in ADPKD. AB - Autosomal-dominant polycystic kidney disease is characterized by the development and expansion of cysts, which ultimately results in kidney failure. The rate of this expansion can now be quantified within a short period of time, which has implications for assessing the risk of renal failure in affected patients. PMID- 19474827 TI - Fibroblast activation and myofibroblast generation in obstructive nephropathy. AB - Obstructive nephropathy is a major cause of renal failure, particularly in newborn babies and children. After urinary tract obstruction, and under the influence of mechanical forces and cytokines produced by tubular cells and cells that have infiltrated the interstitium, resident fibroblasts undergo activation and myofibroblasts are generated from bone-marrow-derived cells, pericytes and endothelial cells. In addition, selected tubular epithelial cells can become fibroblast-like cells via epithelial-mesenchymal transition. This transition is characterized by downregulation of epithelial marker proteins such as E-cadherin, zonula occludens 1 and cytokeratin; loss of cell-to-cell adhesion; upregulation of mesenchymal markers including vimentin, alpha-smooth muscle actin and fibroblast-specific protein 1; basement membrane degradation; and migration to the interstitial compartment. All the events of epithelial-mesenchymal transition are strictly regulated by complex signaling pathways. Myofibroblasts and activated fibroblasts proliferate and produce large amounts of extracellular matrix, which accumulates in the tubular interstitium; together with tubular atrophy, this accumulation leads to interstitial fibrosis. This Review examines the molecular mechanisms of fibroblast activation and epithelial-mesenchymal transition, processes that seem to be promising targets for the prevention, or even reversal, of interstitial fibrosis and renal dysfunction associated with obstructive nephropathy. PMID- 19474830 TI - Analysis of replacing an optical fiber core with polymer. AB - This paper presents the analysis of a 2 cm long in-fiber polymer waveguide formed on the platform of a D-shaped optical fiber. Numerical simulations provide an understanding of the major loss mechanisms for feasible in-fiber polymer waveguide geometries. The primary loss mechanism is determined to be excitation of slab modes on the flat surface of the fiber with transition geometry being the next major contribution to loss. PMID- 19474829 TI - Opinion: Ocular features aid the diagnosis of Alport syndrome. AB - Alport syndrome is a common cause of inherited kidney failure but often goes unrecognized. Most affected families show an X-linked pattern of inheritance where affected males develop renal failure and hearing loss, and often lenticonus and retinopathy. Lenticonus is evident on both ophthalmoscopy and slit-lamp examination but retinal abnormalities are more obvious on imaging. Such abnormalities include a perimacular dot-and-fleck retinopathy and a peripheral fleck retinopathy, which might occur independently of each other; a 'dull macular reflex' or 'lozenge', when the perimacular flecks are confluent; and, rarely, a macular hole caused by retinal thinning. Imaging of the central and peripheral retina including 'red-free' views is a rapid, noninvasive and inexpensive test that might aid the diagnosis of Alport syndrome, particularly in male individuals with early-onset renal failure. The assistance of an interested ophthalmologist is invaluable in the diagnosis of Alport syndrome. PMID- 19474828 TI - Monoclonal antibodies for podocytopathies: rationale and clinical responses. AB - The podocytopathies, including minimal-change nephropathy, focal segmental glomerulosclerosis, collapsing glomerulopathy, and diffuse mesangial sclerosis, involve diverse types of injury to podocytes. These injuries can have genetic causes, or can be caused by viral infection, mechanical stress, medication or probably-immunologic injury. Several lines of evidence-including the immunosuppressive effects of standard therapies-suggest a role for immunologic injury in some cases, but the precise pathologic mechanisms are far from clear. Despite this uncertainty, newly available biologic therapies that target immune cells and cytokines have been used to treat a number of patients with different podocytopathies. Of these therapies, the greatest experience has been gained with rituximab. The data on all such therapies remain too fragmentary to provide firm conclusions, but further clinical research with such agents might help to define pathogenetic pathways and could potentially contribute to new therapies. PMID- 19474831 TI - All-optical AND gate at 10 Gbit/s based on cascaded single-port-couple SOAs. AB - An all-optical logical AND gate at 10 Gbit/s based on cross-gain modulation (XGM) in two cascaded semiconductor optical amplifiers (SOAs) is demonstrated. Single port-coupled SOAs are employed and specially designed to improve the output extinction ratio as well as the output performance of the logic operation. The output signal power and extinction ratio from the first-stage wavelength converter are critical to achieving all-optical logical AND operation. PMID- 19474832 TI - In vivo high-resolution video-rate spectral-domain optical coherence tomography of the human retina and optic nerve. AB - An ultra-high-speed spectral-domain optical coherence tomography system (SD-OCT) was developed for imaging the human retina and optic nerve in vivo at a sustained depth profile (A-line) acquisition speed of 29 kHz. The axial resolution was 6 microm in tissue and the system had shot-noise-limited performance with a maximum sensitivity of 98.4 dB. 3-dimensional data sets were collected in 11 and 13 seconds for the macula and optic nerve head respectively and are presented to demonstrate the potential clinical applications of SD-OCT in ophthalmology. Additionally, a 3-D volume of the optic nerve head was constructed from the acquired data and the retinal vascular network was visualized. PMID- 19474833 TI - Communication modes applied to axicons. AB - The communication modes, which constitute a convenient method for the propagation and information analysis of optical fields, are formulated in the generalized axicon geometry. The transmitting region is the axicon's annular aperture, and the observation domain is the optical axis containing the focal line segment. We show that in rotational symmetry one may employ the prolate spheroidal wave functions to represent the communication modes. Further, in usual circumstances the modes can be approximated by quadratic waves in the aperture domain and by sinc functions in the image domain. Both the exact communication modes and the approximate technique are confirmed numerically, with linear axicons as examples. PMID- 19474834 TI - Primary aberrations in focused radially polarized vortex beams. AB - We study the effect of primary aberrations on the 3-D polarization of the electric field in a focused lowest order radially polarized beam. A full vector diffraction treatment of the focused beams is used. Attention is given to the effects of primary spherical, astigmatic, and comatic aberrations on the local polarization, Strehl ratio, and aberration induced degradation of the longitudinal field at focus. PMID- 19474835 TI - Air-core photonic band-gap fibers: the impact of surface modes. AB - We study the dispersion and leakage properties for the recently reported low-loss photonic band-gap fiber by Smith et al. [Nature 424, 657 (2003)]. We find that surface modes have a significant impact on both the dispersion and leakage properties of the fundamental mode. Our dispersion results are in qualitative agreement with the dispersion profile reported recently by Ouzounov et al. [Science 301, 1702 (2003)] though our results suggest that the observed long wavelength anomalous dispersion is due to an avoided crossing (with surface modes) rather than band-bending caused by the photonic band-gap boundary of the cladding. PMID- 19474836 TI - Improving low-temperature performance of infrared thin-film interference filters utilizing the intrinsic properties of IV-VI narrow-gap semiconductors. AB - Pb(1) (-x)Ge(x)Te is a pseudobinary alloy of IV-VI narrow-gap semiconductor, of which maximum refractive index corresponds to the ferroelectric phase transition. Since the temperature coefficient of refractive index can be tunable from negative to positive by changing the Ge composition, it is possible to utilize the intrinsic property in the fabrication of infrared thin-film interference filters. In this letter, we report a narrow-bandpass filter, in which Pb(0.94)Ge(0.06)Te was substituted for PbTe. It found that the low-temperature stability of the filter is obviously improved: in the temperature range of 80 300K, the shift of center wavelength with temperature is reduced from 0.48nm.K( 1) to 0.23nm K(-1); furthermore, the peak transmittance of filter fabricated with Pb(0.94)Ge(0.06)Te is ~3% over that fabricated with PbTe. PMID- 19474837 TI - Multi-kilowatt, all-fiber integrated chirped-pulse amplification system yielding 40x pulse compression using air-core fiber and conventional erbium-doped fiber amplifier. AB - We present a totally fiber integrated chirped-pulse amplification system using air-core photonic bandgap fiber and a conventional erbium-doped fiber amplifier. ~40-ps input pulses, generated in a Mach-Zehnder modulator, were stretched and spectrally broadened in a dispersion-shifted fiber before being amplified and subsequently compressed in 10 m of anomalously-dispersive photonic bandgap fiber to yield ~960 fs pulses. The system gives multi-kilowatt peak powers while the amplifier nonlinearity threshold is as low as ~150 W. Higher peak powers could be obtained by the use of an amplifier with higher nonlinearity threshold. PMID- 19474838 TI - Effects of bursty traffic in service differentiated Optical Packet Switched networks. AB - Service differentiation is a crucial issue in the next -generation Optical Packet Switched networks. In this paper we examine how bursty traffic influences the performance of a service differentiated Optical Packet Switched network. By using time -continuous Markov chains, we derive explicit results for the packet loss rates in the case of a bursty hyper-exponential arrival process. Results indicate that the performance is degraded as the burstiness of the arrival process increases. PMID- 19474839 TI - 7x 40 Gb/s base-rate RZ all-optical broadcasting utilizing an electroabsorption modulator. AB - We experimentally demonstrate all-optical broadcasting through simultaneous 7 x 40 Gb/s base-rate wavelength conversion in RZ format based on cross absorption modulation in an electroabsorption modulator. In this experiment the original intensity-modulated information is successfully duplicated onto seven wavelengths that comply with the ITU-T proposal. The advantages of the proposed wavelength conversion scheme are also discussed. PMID- 19474840 TI - Viewing-angle-enhanced integral imaging system using a curved lens array. AB - We propose an enhanced three-dimensional integral imaging system using a curved lens array. Incorporation of a curved lens array instead of a conventional flat lens array expands the viewing angle remarkably. The flipped images are eliminated effectively by adopting barriers. The principle of the proposed system is explained and the experimental results are also presented. PMID- 19474841 TI - Bandwidth comparison of photonic crystal fibers and conventional single-mode fibers. AB - We experimentally compare the optical bandwidth of a conventional single-mode fiber (SMF) with 3 different photonic crystal fibers (PCF) all optimized for visible applications. The spectral attenuation, single-turn bend loss, and mode field diameters (MFD) are measured and the PCF is found to have a significantly larger bandwidth than the SMF for an identical MFD. It is shown how this advantage can be utilized for realizing a larger MFD for the PCF while maintaining a bending resistant fiber. PMID- 19474842 TI - Raman amplifier design using geometry compensation technique. AB - We propose a simple technique to optimize a multi-wavelength backward-pumped fiber Raman amplifier. Based on the geometric characteristics of Raman gain profile, we approximate it using several straight lines and utilize slope compensation technique to achieve flat and wideband gain profile. Good simulation results are obtained. PMID- 19474843 TI - Extinction-ratio-independent method for chirp measurements of Mach-Zehnder modulators. AB - The authors describe a general method to extract the frequency chirping of Mach Zehnder modulators based on direct measurements of the output spectrum. This method is independent of the modulator extinction ratio and allows measurement of the intrinsic chirp parameter to an accuracy of 5%. PMID- 19474844 TI - Fast 3-d optical imaging with transient fluorescence signals. AB - A fast 3-D optical imaging method with use of exogenous fluorescence agent is proposed and demonstrated by simulation in a model tissue. After administration of fluorescent agent, ultrashort near-infrared laser pulses are used to illuminate the tissue and excite fluorescence emission. The transient fluorescence signals are detected on the tissue boundaries and employed to reconstruct a 3-D image of relative fluorescence emission distribution inside the tissue. A region with greater fluorescence emission represents a diseased tissue if the fluorescent agent has a close affinity with the disease. We successfully demonstrated the feasibility of this method in the imaging of a 4x4x4mm(3) tumor embedded at the center of a cubical tissue phantom with an uptake distribution of fluorescent indocyanine green dye. The image reconstruction does not involve any inverse problem. It took less than 5 minutes in a PC for the model imaging problem. PMID- 19474845 TI - Two physical mechanisms for boosting the quality factor to cavity volume ratio of photonic crystal microcavities. AB - We identify two physical mechanisms which drastically increase the Q/V factor of photonic crystal microcavities. Both mechanisms rely on a fine tuning the geometry of the holes around the cavity defect. The first mechanism relies on engineering the mirrors in order to reduce the out-of-plane far field radiation. The second mechanism is less intuitive and relies on a pure electromagnetism effect based on transient fields at the sub-wavelength scale, namely a recycling of the mirror losses by radiation modes. The recycling mechanism enables the design of high-performance microresonators with moderate requirements on the mirror reflectivity. Once the geometry around the defect is optimised, both mechanisms are shown to strongly impact the Q and the Purcell factors of the microcavity. PMID- 19474846 TI - Photonic crystal fiber with a hybrid honeycomb cladding. AB - We consider an air-silica honeycomb lattice and demonstrate a new approach to the formation of a core defect. Typically, a high or low-index core is formed by adding a high-index region or an additional air-hole (or other low-index material) to the lattice, but here we discuss how a core defect can be formed by manipulating the cladding region ratherthan the core region itself. Germanium doping of the honeycomb lattice has recently been suggested for the formation of a photonic band-gap guiding silica-core and here we experimentally demonstrate how an index-guiding silica-core can be formed by fluorine-doping of the honeycomb lattice. PMID- 19474847 TI - Pulse trains produced by phase-modulation of ultrashort optical pulses: tailoring and characterization. AB - In this paper, creation of pulse doublets and pulse trains by spectral phase modulation of ultrashort optical pulses is investigated. Pulse doublets with specific features are generated through step-like and triangular spectral phase modulation, whereas sequences of pulses with controllable delay and amplitude are produced via sinusoidal phase modulations. A temporal analysis of this type of tailored pulses is exposed and a complete characterization with the SPIDER technique (Spectral Phase Interferometry for Direct Electric-field Reconstruction) is presented. PMID- 19474848 TI - Three-dimensional volumetric object reconstruction using computational integral imaging. AB - We propose a three-dimensional (3D) imaging technique that can sense a 3D scene and computationally reconstruct it as a 3D volumetric image. Sensing of the 3D scene is carried out by obtaining elemental images optically using a pickup microlens array and a detector array. Reconstruction of volume pixels of the scene is accomplished by computationally simulating optical reconstruction according to ray optics. The entire pixels of the recorded elemental images contribute to volumetric reconstruction of the 3D scene. Image display planes at arbitrary distances from the display microlens array are computed and reconstructed by back propagating the elemental images through a computer synthesized pinhole array based on ray optics. We present experimental results of 3D image sensing and volume pixel reconstruction to test and verify the performance of the algorithm and the imaging system. The volume pixel values can be used for 3D image surface reconstruction. PMID- 19474849 TI - Change in PMD due to the combined effect of PMD and PDL for a chirped Gaussian pulse. AB - The nature of how a chirped Gaussian pulse is affected in the system with both polarization mode dispersion (PMD) and polarization-dependent loss (PDL) is analyzed. We develop a mathematical description and verify the results through numerical simulation. The delay of a chirped Gaussian pulse depends not only on the group delay characteristic of the transmission system but also on the chirp of the pulse itself. The delay also depends on the magnitude profile of the frequency response of the system. Therefore, the effective PMD for a chirped Gaussian pulse is related to both the PMD and PDL in the transmission system. The results show that the effective PMD may deteriorate when a PDL exists. PMID- 19474850 TI - Continuous-wave pump-enhanced optical parametric oscillator with ring resonator for wide and continuous tuning of single-frequency radiation. AB - We demonstrate a PPLN based pump-enhanced, singly-resonant optical parametric oscillator configured in a traveling wave geometry and pumped by a Ti:sapphire laser. The inclusion of a low finesse etalon within the OPO cavity stabilizes the signal frequency, and rotation of the etalon allows this frequency to be systematically hopped from axial mode to nearest neighbor axial mode over the entire free spectral range of the etalon (83GHz). Tuning of the pump frequency allows the signal frequency to be smoothly tuned over a cavity free spectral range. More than 35mW of single frequency idler power was generated in the spectral range 2800-3000nm for 600mW pump power. The superiority of traveling wave over standing wave geometries in these regards is discussed. PMID- 19474851 TI - Spherical object in radiation field from a point source. AB - A general formula for calculating radiative fluxes from point sources of radiation incident on spherical objects was derived using some fundamental laws of classical radiometry. This formula was derived in the Cartesian coordinate system, 0xyz, where the coordinates, x, y, and z, determine the position of the spherical object with respect to the point source. The obtained solution was dependent on the radius of the object, and on the function describing the intensity of the radiation. A specific solution for calculating fluxes of isotropic radiations was presented and selected calculations were illustrated graphically. PMID- 19474852 TI - Ultra-broadband chirped-pulse optical parametric amplifier with angularly dispersed beams. AB - We propose a BBO-based chirped-pulse optical parametric amplifier employing an angularly dispersed signal beam to yield a full-octave gain bandwidth, sufficient for the direct amplification of sub-10-fs pulses. Numerical simulations show that this power-scalable amplifier configuration has a small-signal gain of 10(7) at a pumping intensity of 45 GW/cm(2). The additional phase-matching flexibility compared to alternative configurations permits the suppression of parasitic second harmonic generation of the signal beam. PMID- 19474853 TI - Use of a genetic algorithm to optimize multistage erbium-doped fiber-amplifier systems with complex structures. AB - We propose optimizing multifunctional multistage erbiumdoped fiber amplifiers (EDFAs) with complex structures by use of a genetic algorithm. With this method, we investigated optimum configurations of C- and L-band gain-flattened multistage EDFAs containing gain-flattening filters and high-loss interstage elements for dense wavelength-division multiplexing systems in detail and compared the amplifiers with various kinds of configurations under different design criteria. With the guidance of optimization results, the roles of all the factors such as pumping schemes, pump-power allocation, component position, and insertion loss in the optimization of EDFAs have been studied, and useful guidelines for optimizations have been provided. PMID- 19474854 TI - Powerful solution for simulating nonlinear coupled equations describing bidirectionally pumped broadband Raman amplifiers. AB - A mid-point shooting algorithm using the Newton-Raphson method is adopted for solving nonlinear coupled equations describing bidirectionally pumped broadband Raman amplifiers. A series of novel backward-differentiation methods are constructed for the first time to our knowledge. Their combination can form a powerful solution for fiber amplifiers. Numerical results show that the approach can solve Raman amplifier propagation equations on various conditions including co-, counter-, and bidirectionally pumped cases. The computation speed of the present methods is about four times that of the backward-differentiation methods previously adopted. PMID- 19474855 TI - Atomic mercury flux monitoring using an optical parametric oscillator based lidar system. AB - A newly developed optical parametric oscillator (OPO) based differential absorption lidar (DIAL) system has been applied to the monitoring of atomic mercury emissions at several chlor-alkali plants in Europe. The versatility of the system is illustrated by measured time series of mercury flux and movies of vertical and horizontal concentration distributions, which yield important input parameters for the environmental community. Long term measurements of the resonance absorption of mercury at 253.65 nm poses special demands, i.e. long term stability, on the light source that often have been hard to fulfill, in different respects, for standard OPO and dye laser based systems. Here, approaches to meet these demands are presented. PMID- 19474856 TI - Spatiotemporally multiplexed integral imaging projector for large-scale high resolution three-dimensional display. AB - We present a projection method in integral imaging for large-scale high resolution three-dimensional display. In the proposed method, the entire set of high resolution elemental images with a large number of pixels is spatially divided into smaller image subsets. Then they are projected separately onto the corresponding lenslet array positions either simultaneously or in a sequence faster than the flicker fusion frequency of human eyes or both (i.e., spatiotemporal multiplexing). Thus display panels that do not have enough pixel numbers can be used to display the entire elemental images with a large number of pixels. Preliminary experiments were performed using a galvanometer-based optical scanner. PMID- 19474857 TI - Efficient algorithm and optimization for broadband Raman amplifiers. AB - A hybrid genetic algorithm (HGA) assisted by stochastic perturbation and the adaptive technique is proposed. Compared with our previous reports, the proposed HGA can exploit better solutions and greatly shorten the amount of run time. An example shows that the design of multipump Raman amplifiers involves the multimodal function optimization problem with multiple variables. With the new HGA, relationships of the optimal signal bandwidth with the span length and the ON-OFF Raman gain are obtained. A movie demonstrates the detailed interaction in pump-to-signal and signal-to-signal procedures. The corresponding optical signal to-noise ratio of optimal results is obtained. PMID- 19474858 TI - Sub femto-joule sensitive single-shot OPA-XFROG and its application in study of white-light supercontinuum generation. AB - We report a new design of single-shot cross-correlation frequency-resolved optical gating (XFROG) with sub femto-joule sensitivity for complete field characterization of ultrashort optical pulse using a 400- nm-pumped type-I noncollinear optical parametric amplifier. Optical parametric gain as high as 10(8) with 0.8-0.9 femto-joules sensitivity had been demonstrated with an un cooled CCD in this study. The experimental FROG traces have been successfully retrieved with an error no worse than 0.0014. The device had been to be useful for studying the generation mechanism of white-light supercontinuum (WLS). PMID- 19474859 TI - Complex intensity modulation transfer function for supercontinuum generation in microstructure fibers. AB - We investigated the complex intensity modulation transfer function for supercontinuum generation in microstructure fibers (MSF). We measured the relative intensity and phase modulations in the output spectrum of the MSF with spectral resolution of one and ten nanometers, respectively. For small intensity modulation indices (~ 1 %) we found power modulation gain factors as large as 100 in certain spectral areas of the super continuum. In all spectral regions the phase modulation coefficient was found not to exceed 40 rad per percent of pulse power change. Consequences for applications of phase-coherent supercontinua, such as frequency metrology, pulse synthesis, heterodyne coherent anti-Stokes Raman scattering (CARS) are discussed. PMID- 19474860 TI - 2D Photonic crystal thermo-optic switch based on AlGaAs/GaAs epitaxial structure. AB - The realisation of a thermo-optically controlled symmetric Mach- Zehnder interferometer switch based on an AlGaAs/GaAs epitaxial waveguide structure operating at wavelengths in the region of lambda = 1550 nm is reported. The device is based on a very compact two-dimensional photonic crystal channel waveguide structure. The measured and simulated transmission spectra for the devices are in good agreement. The Pi-phase shift switching power for the device is as low as 42 mW. PMID- 19474861 TI - Manipulation and filtration of low index particles with holographic Laguerre Gaussian optical trap arrays. AB - Multiple low index particles (micrometer-sized ultrasound contrast agent), have been optically trapped using a 4 x 4 Laguerre- Gaussian trap array. The trapping efficiency of the Laguerre-Gaussian arrangement was measured using a Stokes' flow approach whereby the critical relative fluid velocity required to remove particles from the optical trap was measured. The dependence of trapping efficiency on beam power was also explored and the optimum beam parameters were identified. Finally, the utility of the array as a selective filter was demonstrated by tweezing multiple low-index particles from a population exhibiting an inherent distribution in size. This procedure represents a unique remote non-contact process that may have significant applicability throughout the fields of biophysics and biotechnology. PMID- 19474862 TI - Multi-port polarization-independent optical quasi-circulators by using a pair of holographic spatial- and polarization- modules. AB - In this paper we proposed an alternative type of multi-port polarization independent optical quasi-circulator by using a pair of holographic spatial- and polarization- modules. The prototype is fabricated and experimentally tested. In addition, the operating principles, the characteristics and the performances of this device are discussed. The merits of this design include polarization independence, compactness, high isolation, low polarization mode dispersion, and easy fabrication. Furthermore, the number of ports can be scaled up easily. PMID- 19474863 TI - Improvement of spatial and temporal coherence of a broad area laser diode using an external-cavity design with double grating feedback. AB - We demonstrate a novel technique for narrow bandwidth and highly improved lateral mode operation of a high-power broad area laser diode. The system uses simultaneous feedback from the first diffracted order and the zeroth reflected order of a diffraction grating. The two feedback paths lead to simultaneously improvement of the spectral and spatial properties of the laser diode. The laser system operates in the well-known asymmetric double-lobed far field pattern with the larger lobe being extracted as the output. The bandwidth of the output beam is measured to 0.07 nm, which corresponds to an improvement of a factor of 17 compared to the bandwidth of the freely running laser. The output from the system contains 54% of the energy reaching the grating, or 75% of the power reflected into the zeroth order. The improvements in both the spatial and temporal coherence opens the possibility of using this laser system in applications such as frequency doubling and pumping of optical parametric oscillators. PMID- 19474864 TI - Nanopillars photonic crystal waveguides. AB - We present a novel type of a waveguide, which consists of several rows of periodically placed dielectric cylinders. In such a nanopillars photonic crystal waveguide, light confinement is due to the total internal reflection, while guided modes dispersion is strongly affected by waveguide periodicity. Nanopillars waveguide is multimode, where a number of modes is equal to the number of rows building the waveguide. We present a detailed study of guided modes properties, focusing on possibilities to tune their frequencies and spectral separation. An approach towards the specific mode excitation is proposed and prospects of nanopillars waveguides application as a laser resonator are discussed. PMID- 19474865 TI - Spectral analysis of resonant transmission of light through a single sub wavelength slit. AB - We analyze the spectral properties of resonant transmission of light through a sub-wavelength slit in a metal film. We show that the enhanced transmission can be understood in terms of interfering surface-wave-like modes propagating in the slit. We characterize the effect of geometrical and material properties of the slit on the transmission spectrum. Furthermore, we show that the wavelength of the transmission resonance strongly depends on the surrounding medium. This effect may be utilized in sensors, imaging, and the detection of, e.g. biomolecules. PMID- 19474866 TI - Performance analysis of three dimensional high index contrast dielectric waveguides. AB - This paper presents the implementation of a parallelized Finite- Difference Time Domain method, based on the Message Passing Interface (i.e. MPI), which is used to study the modal properties of three-dimensional (3D) dielectric waveguide structures. To this end, we also use the leastsquare method to obtain the wave vector, beta, along the axis of propagation. Lastly, bending losses in arbitrary angle waveguides are also discussed. PMID- 19474867 TI - Modulation-free sub-Doppler laser frequency stabilization to molecular iodine with a common-path, two-color interferometer. AB - Recently, a simple common-path, two-color interferometer has been used for Doppler-free saturated dispersion spectroscopy of iodine. We have used such a set up to stabilize a Nd:YAG laser for the first time, to our knowledge. This method requires only a small number of low-cost optical components compared to frequency modulation techniques.We have measured a root Allan variance of 5 . 10(-12) for 0.2 s, and below 5 . 10 (-11) for integration times up to 300 s. PMID- 19474868 TI - All-optical switching application based on optical nonlinearity of Yb(3+) doped aluminosilicate glass fiber with a long-period fiber gratings pair. AB - We propose a new fiber-type all-optical switching device based on the optical nonlinearity of Yb(3+) doped fiber and a long-period fiber gratings(LPG) pair. The all-optical ON-OFF switching with the continuous wave laser signal at ~1556nm in the LPG pair including the 25.5cm long Yb(3+) doped fiber was demonstrated up to ~200Hz upon pumping with the modulated square wave pulses at 976nm, where a full optical switching with the ~18dB extinction ratio was obtained at the launched pump power of ~35mW. PMID- 19474869 TI - Mie scattering analysis of spherical Bragg "onion" resonators. AB - Combining the Mie scattering theory and a transfer matrix method, we investigate in detail the scattering of light by spherical Bragg "onion" resonators. We classify the resonator modes into two classes, the core modes that are confined by Bragg reflection, and the cladding modes that are confined by total internal reflection. We demonstrate that these two types of modes lead to significantly different scattering behaviors. PMID- 19474870 TI - Optical trapping and fluorescence excitation with violet diode lasers and extended cavity surface emitting lasers. AB - Violet diode lasers and vertical extended cavity surface emitting lasers are used within an optical trapping system. Two distinct but related studies are performed. Firstly, the optical trapping efficiency in terms of the Q parameter for micron and sub-micron sized particles is determined. Secondly, we use the violet diode laser to observe and fluoresce 4'-6- Diamidino-2-phenylindole (DAPI) stained chromosomes, green fluorescent protein (GFP) transfected neuroblastomas, and fluorescent polymer spheres within an optical tweezers using a 1064nm trap laser. This work paves the way for both reduced trap volumes and for biological tagging, chromosome selection, or observing protein dynamics. PMID- 19474871 TI - Cross-coherence measurements of supercontinua generated in highly-nonlinear, dispersion shifted fiber at 1550 nm. AB - We present measurements of cross-coherence between independent supercontinua, generated at 1550 nm. An all-fiber supercontinuum source, consisting of a femtosecond fiber laser, fiber amplifier, and highlynonlinear dispersion shifted fiber is characterized. Supercontinua generated from both 2 picosecond and 188 femtosecond pump pulses are considered. The continua generated with picosecond pulses show a degradation in coherence as the pump power is increased, whereas a high degree of cross-coherence over a broad wavelength range can be maintained when femtosecond pulses are used. PMID- 19474872 TI - Effect of frequency chirping on supercontinuum generation in photonic crystal fibers. AB - Pre-chirp of the input pulse has a significant effect on pulse evolution in a photonic crystal fiber. We present numerical simulations which show that the supercontinuum bandwidth increases with the linear chirp, and that the coherence of supercontinuum improves as frequency chirping increases. An optimal positive chirp is identified that maximizes the supercontinuum bandwidth, corresponding to the formation of only one red-shifting Raman soliton. PMID- 19474873 TI - Highly efficient white light generation from barium fluoride. AB - We demonstrate highly efficient white light generation by focusing 45 fs long pulses of 800 nm laser radiation with 1 mJ energy onto a 10 cm long barium fluoride crystal. The entire wavelength band from 400-1000 nm was generated with efficiency greater than 40%. We also observe multiphoton absorption induced fluorescence in the crystal. By employing line focusing geometry at low intensity, we show that white light fringes are formed with a single laser beam, indicative of the coherent property of the white light that is produced. PMID- 19474874 TI - Wavelength selective single and dual-channel dropping in a periodically poled Ti:LiNbO(3) waveguide. AB - All-optical wavelength selective single and dual channel dropping by sum frequency generation has been demonstrated in a periodically poled Ti:LiNbO(3) waveguide, which has two second harmonic phase-matching peaks. Less than -17 dB of channel dropping extinction ratio was observed with coupled pump power of 325 mW. PMID- 19474875 TI - Transverse modulational instabilities of counterpropagating solitons in photorefractive crystals. AB - We study numerically the counterpropagating vector solitons in SBN:60 photorefractive crystals. A simple theory is provided for explaining the symmetry breaking transverse instability of these solitons. Phase diagram is produced that depicts the transition from stable counterpropagating solitons to bidirectional waveguides to unstable optical structures. Numerical simulations are performed that predict novel dynamical beam structures, such as the standing-wave and rotating multipole vector solitonic clusters. For larger coupling strengths and/or thicker crystals the beams form unstable self-trapped optical structures that have no counterparts in the copropagating geometry. PMID- 19474876 TI - High energy nanosecond laser pulses delivered single-mode through hollow-core PBG fibers. AB - We report on the development of hollow-core photonic bandgap fibers for the delivery of high energy pulses for precision micromachining applications. Short pulses of (65ns pulse width) and energies of the order of 0.37mJ have been delivered in a single spatial mode through hollow-core photonic bandgap fibers at 1064nm using a high repetition rate (15kHz) Nd:YAG laser. The ultimate laser induced damage threshold and practical limitations of current hollow-core fibers for the delivery of short optical pulses are discussed. PMID- 19474877 TI - Discrimination of temperature and strain with a single FBG based on the birefringence effect. AB - We will demonstrate a new technique to discriminate the temperature and strain effects using a single fiber Bragg grating (FBG). The birefringence is typically induced during FBG inscription, and it is manifested as polarization-dependent loss (PDL), and it is defined as the maximum change in the transmitted power for polarizations. Two independent measurements of the resonance wavelength shift and the changes of PDL can discriminate those effects. PMID- 19474878 TI - Mode-controlled colors from microstructure fibers. AB - We experimentally demonstrate mode-controlled spectral transformation of femtosecond laser pulses in microstructure fibers. Depending on the waveguide mode excited in the fiber, 30-fs Ti: sapphire laser pulses can either generate a broadband emission or produce isolated spectral components in the spectrum of output radiation. This method is used to tune the frequencies dominating the output spectra, controlled by phase matching for four-wave mixing processes. PMID- 19474879 TI - Origin of power fluctuations in GaN resonant-cavity light-emitting diodes. AB - Resonant-cavity light-emitting diodes (RCLEDs) with multiple InGaN/GaN quantum wells have been grown on sapphire substrates. The emission was through the substrate, and the top contact consisted of a highly reflecting Pd/Ag metallization. The peak emission wavelength was measured to be 490 nm. Under constant current biasing, the intensity was observed to fluctuate irregularly accompanied by correlated variations in the voltage. To investigate this further, emission from the RCLED was focused through a GaAs wafer onto a Vidicon camera. This gave a series of infrared, near-field images, spectrally integrated over a wavelength range from 870 nm to 1.9 microm. Flashes from point sources on the RCLED surface were observed, indicating that short-lived, highly localized "hot spots" were being formed that generated pulses of thermal radiation. It is proposed that this phenomenon results from the migration of metal into nanopipes present in this material. The filled pipes form short circuits that subsequently fuse and are detected by bursts of infrared radiation that are recorded in real time. PMID- 19474880 TI - Fabrication of internal diffraction gratings in calcium fluoride crystals by a focused femtosecond laser. AB - We report the fabrication of internal diffraction gratings in calcium fluoride crystals by a focused near-IR 800 nm femtosecond laser. The diffraction efficiency and refractive index change were evaluated after femtosecond laser irradiation and subsequent annealing. The maximum refractive index change was estimated to be 3.57x10(-4). Optical absorption spectra, measured for the crystals before and after the laser irradiation and subsequent annealing, indicate that the absorbance increase after femtosecond laser irradiation and decrease with increasing annealing temperature. The mechanisms of refractive index change are proposed. The results may be useful for fabrication of three dimensional integrated optics devices in the crystals. PMID- 19474881 TI - Monomode optical waveguide excited at 1540 nm in LiNbO(3) formed by MeV carbon ion implantation at low doses. AB - The monomode enhanced-index LiNbO(3) waveguide excited at 1540 nm is reported. X cut LiNbO(3) crystals were implanted at room temperature by 6.0 MeV C(3+) ions with a dose of 2.0x10(15) ions/cm(2). Low loss planar optical waveguides were obtained and characterized by the prism coupling technique. Four dark modes were observed for extraordinary light at 633 nm, while only one enhanced-index mode was observed at 1540 nm. The propagation loss of the waveguide is 1.01 dB/cm measured with the moving fiber method. Reflectivity calculation method (RCM) was applied to simulate the refractive index profiles in waveguide. The width of waveguide structure induced by carbon ion implantation is ~3.6 microm. PMID- 19474882 TI - Double-pass Fourier transform imaging spectroscopy. AB - Fourier-Transform Imaging Spectroscopy (FTIS) has recently become a widely used tool for spectral imaging of biological fluorescent samples. Here we report on a novel double-pass FTIS system, that is capable of obtaining an excitation as well as an emission spectrum of the fluorescent sample with only a single sweep of the interferometer. This is achieved by modifying an existing FTIS system, placing the excitation source before the interferometer so as to spectrally modulate the excitation as well as the detection. An analysis of the acquired signal allows for the reconstruction of the excitation as well as the emission spectrum of each fluorophore assuming an independence of the two spectra for each fluorophore. Due to the patterned excitation generated by the Sagnac interferometer a substantial degree of optically sectioning is achieved at excitation wavelengths. Further analysis of the acquired data also enables the generation of optically sectioned emission images. A theoretical analysis and experimental data based on fluorescent beads are presented. PMID- 19474883 TI - Experimental demonstration of cascaded AWG access network featuring bi directional transmission and polarization multiplexing. AB - We present the first experimental demonstration of a bidirectional cascaded arrayed-waveguide grating (AWG) access network combining one NxN AWG in the central office with multiple 1xN AWG's at the distribution points, such as to individually address N(2) users with only N wavelengths. Downstream and upstream data share the same optical path. BER curves were measured using 2.5Gb/s data stream in each direction, and error free transmission achieved for downstream and upstream, with only 0.3dB power penalty for simultaneous transmission. The addition of two orthogonal polarization-multiplexed channels per wavelength doubled the number of possible end users. Error free transmission was achieved with simultaneous upstream and downstream transmission of a composite signal featuring eight 2.5Gb/s channels (2 polarizations x 4 wavelengths). PMID- 19474884 TI - Phase-locked carrier-envelope-offset frequency at 1560 nm. AB - We report on the measurement of an Erbium-fiber oscillator's carrier-envelope offset frequency using an extruded SF6 photonic crystal fiber for the generation of a more than two octave-spanning supercontinuum from 400 nm to beyond 1750 nm. A modified type of f-2f-interferometer was employed, beating the frequency doubled input signal of the fiber oscillator with the supercontinuum to generate the carrier-envelope-offset beat. Controlling the fiber oscillator's pump power with an electronic feedback loop, we phase-locked the carrier-envelope-offset frequency to an external reference source. The resulting residual phase excursions correspond to fractional frequency instabilities of the oscillator's frequency comb of the order of 10(-16) for averaging times longer than 10 s. PMID- 19474885 TI - Tapered photonic crystal fibers. AB - We demonstrate the tapering of a photonic crystal fiber to achieve a microstructure pitch of less than 300 nm. We probe the tapered fiber in the transverse geometry to demonstrate the scaling of the photonic bandgaps associated with the microstructure. We show that the fundamental gap can be shifted down to the communications wavelengths, or even further to the visible spectrum. Our optical measurements are correlated with band structure calculations. PMID- 19474886 TI - Efficient, all-solid-state, Raman laser in the yellow, orange and red. AB - We report efficient operation of a KGd(WO(4))(2) Raman laser pumped by a small, 1 W, 532 nm laser module. By changing the output coupler and Raman crystal orientation, more than 8 wavelengths in the yellow-to-red spectral region were generated including 555 nm, 559 nm, 579 nm, 589 nm, 606 nm, 622 nm, 636 nm and 658 nm, ie., the first 4 Stokes orders on the two orthogonal high-gain Raman shifts of KGd(WO(4))(2). We have also demonstrated spectrally pure output (typically >90% pure) for selected Stokes order with output power up to 400 mW. High slope efficiency (up to 68%) and high beam quality (M(2)~1.5) of Stokes output are obtained even at the highest pump power. PMID- 19474887 TI - Experimental studies of polarization properties of supercontinua generated in a birefringent photonic crystal fiber. AB - Besides coherence degradations, supercontinuum spectra generated in birefringent photonic crystal fibers also suffer from polarization fluctuations because of noise in the input pump pulse. This paper describes an experimental study of polarization properties of supercontinuum spectra generated in a birefringent photonic crystal fiber, validating previous numerical simulations. PMID- 19474888 TI - Analysis for long period fiber gratings using thermal kernel function. AB - To analyze the various LPFGs with thermal changes, we present how makes the kernel function to translate the information of thermal change into the coupling coefficient and detuning factor changed by temperature. We propose the extended fundamental matrix model with the proposed kernel function. To verify the validity of the proposed model experimentally, we have manufactured the LPFG structures with the thermal changes using the divided coil heater. We have observed that the transmission spectra calculated using the proposed model are close to the corresponding measured spectra in the wavelength band of interest. PMID- 19474889 TI - Spectral properties of second-harmonic generation at 800 nm in a BiB(3)O(6) crystal. AB - We have investigated spectral distribution and walk-off effect of second-harmonic generation in a 3-mm-long type I BiB(3)O(6) crystal. Linearly turning ability of the BiB(3)O(6) crystal is confirmed for wavelengths around 800 nm. In addition, the walk-off effect of fundamental beams is quantitatively measured by introducing a little vertical polarization component into pumping fundamental pulses. A conversion efficiency of 28% from fundamental to second harmonic is achieved at a 3.2-GW/cm(2) fundamental intensity. PMID- 19474890 TI - Vortex solitons in photonic crystal fibers. AB - We demonstrate the existence of vortex soliton solutions in photonic crystal fibers. We analyze the role played by the photonic crystal fiber defect in the generation of optical vortices. An analytical prediction for the angular dependence of the amplitude and phase of the vortex solution based on group theory is also provided. Furthermore, all the analysis is performed in the non paraxial regime. PMID- 19474891 TI - Optical parametric oscillations in isotropic photonic crystals. AB - We investigate optical parametric oscillations via four-wave mixing in a dielectric photonic crystal. Using a fully vectorial 3D time-domain approach, including both dispersion and Kerr nonlinear polarization, we analyze the response of an inverted opal. The results demonstrate the feasibility of parametric sources in isotropic media arranged in photonic band-gap geometries. PMID- 19474892 TI - Self-phase-modulation induced spectral broadening in silicon waveguides. AB - The prospect for generating supercontinuum pulses on a silicon chip is studied. Using ~4ps optical pulses with 2.2GW/cm(2) peak power, a 2 fold spectral broadening is obtained. Theoretical calculations, that include the effect of two photon-absorption, indicate up to 5 times spectral broadening is achievable at 10x higher peak powers. Representing a nonlinear loss mechanism at high intensities, TPA limits the maximum optical bandwidth that can be generated. PMID- 19474893 TI - Femtosecond soliton pulse delivery at 800nm wavelength in hollow-core photonic bandgap fibers. AB - We describe delivery of femtosecond solitons at 800nm wavelength over five meters of hollow-core photonic bandgap fiber. The output pulses had a length of less than 300fs and an output pulse energy of around 65nJ, and were almost bandwidth limited. Numerical modeling shows that the nonlinear phase shift is determined by both the nonlinearity of air and by the overlap of the guided mode with the glass. PMID- 19474894 TI - Aperiodic 1-dimensional structures for quasi-phase matching. AB - We describe a method for designing 1-dimensional aperiodic poled grating structures of finite length that quasi-phase match multiple Chi((2)) processes. The poling functions for such gratings are best aligned, in terms of the dot product in Fourier space, with a design target. No restrictions are placed on the quasi-phase matching wave numbers. A grating designed for third harmonic generation is simulated. PMID- 19474895 TI - Structure and propagation of modes of large mode area holey fibers. AB - We report cross-section measurement and propagation measurement of modes of large mode area holey fibers using near-field scanning optical microscopy (NSOM). Mode profiles are measured at the fiber end face using a scanning optical fiber tip held 10 nm from the surface, and compared to theoretical models. Both amplitude and phase of the electric field of the propagating light is measured using NSOM techniques as a function of distance from the fiber end, from 10 nm to 150 microm. Good agreement is found between the data and simple scalar paraxial beam propagation simulations of theoretical mode profiles. PMID- 19474896 TI - Detection of biological tissue in gels using pulsed digital holography. AB - An out of plane optical sensitive configuration for pulsed digital holography was used to detect biological tissue inside solid organic materials like gels. A loud speaker and a shaker were employed to produce a mechanical wave that propagates through the gel in such a way that it generates vibrational resonant modes and transient events on the gel surface. Gel surface micro displacements were observed between the firing of two laser pulses, both for a steady resonant mode and for different times during the transient event. The biological tissue sample inserted approximately 2 cm inside the gel diffracts the original mechanical wave and changes the resonant mode pattern or the transient wave on the gel surface. This fact is used to quantitatively measure the gel surface micro displacement. Comparison of phase unwrapped patterns, with and without tissue inside the gel, allows the rapid identification of the existence of tissue inside the gel. The results for the resonant and transient conditions show that the method may be reliably used to study, compare and distinguish data from inside homogeneous and in-homogeneous solid organic materials. PMID- 19474897 TI - Transverse mode control by etch-depth tuning in 1120-nm GaInAs/GaAs photonic crystal vertical-cavity surface-emitting lasers. AB - Robust and tolerant single-transverse-mode photonic crystal GaInAs vertical cavity surface-emitting lasers are fabricated and investigated. Triangular lattice patterns of rectangular air holes of various etch-depths are introduced in the top mirror. The stable single-transversemode operation is observed with a large margin of allowance in the etch depth (t = 2.5 +/- 0.6 microm). This stable mode selection mechanism is explained by the mode competition between the two lowest photonic crystal guided modes that are influenced by both the index guiding effect and the etchdepth dependent modal losses. PMID- 19474898 TI - Demonstration of 3-dimensional wide angle laser beam scanner using liquid crystals. AB - Design and demonstration of a versatile liquid crystal-based scanner is shown for steering a laser beam in three dimensions. The scanner consists of a unique combination of digital and analog control polarization-based beam forming optics resulting in both continuous and random fashion beam steering. The design features a novel device biasing method, large aperture beam-forming optics, low electrical power consumption, and ultrafine as well as wide angle coarse beam steering. Demonstrations include one, two and three dimensional beam steering with a maximum of 40.92 degree continuous scan, all at 1550 nm. The minimum scanner aperture is 1 cm diameter and uses a combination of ferroelectric and nematic liquid crystals in addition to Rutile crystal birefringent prisms. PMID- 19474899 TI - Dynamic near-field calculations of surface-plasmon polariton pulses resonantly scattered at sub-micron metal defects. AB - We investigate theoretically the near-field dynamics of the scattering of a surface-plasmon polariton (SPP) pulse impinging normally on a rectangular groove on an otherwise planar metal surface. Our formulation is based on solving the reduced Rayleigh equation (derived through the use of an impedance boundary condition) for every component of the spectral decomposition of the incoming SPP pulse. Numerical calculations are carried out of the time dependence of the near field resonant scattering effects produced at the rectangular groove. The scattering process is tracked through the (time-resolved) repartition of the incoming SPP electromagnetic energy into reflected and transmitted SPP pulses, and into pulsed scattered light. Furthermore, we directly show evidence of the excitation of single resonances, as manifested by the concentration of electric field intensity within the groove, and its subsequent leakage, over the resonance lifetime. The near-field formation of oscillations caused by the interference between two adjacent resonances simultaneously excited is also considered. PMID- 19474900 TI - All-optical switching characteristics in bacteriorhodopsin and its applications in integrated optics. AB - We experimentally and theoretically investigated the optical switching characteristics of bacteriorhodopsin (bR) at lambda=633 nm using the pump-probe method. A diode-pumped second harmonic YAG laser (lambda=532 nm which is located around the maximum initial Br state absorption) was used as a pumping beam and a cw He-Ne laser (lambda=633 nm which is around the peaks of K and O states) was used as a probe. Due to the nonlinear intensity induced excited state absorption of the K, L, M, N, and O states in the bR photocycle, the switching characteristics are sensitive to the intensity of the probe and pump beams. Based on this property, we have demonstrated an all-optical device functioning as 11 kinds of variable binary all-optical logic gates. PMID- 19474901 TI - Pulse-amplitude equalization in a rational harmonic mode-locked semiconductor fiber ring laser using a dual-drive Mach-Zehnder modulator. AB - We present and demonstrate a simple method of pulse-amplitude equalization in a rational harmonic mode-locked semiconductor ring laser, using a dual-drive Mach Zehnder (MZ) modulator. Pulse-amplitude equalization was achieved by adjusting the voltages applied to both arms of the modulator, such that each mode-locked pulse experiences the same transmission coefficient in the transmission curve of the modulator. With this method, amplitude-equalized pulse trains with repetition rates of ~7.41GHz (third rational harmonic) and ~12.34GHz (fifth rational harmonic) were successfully obtained without any additional function to the ring laser itself. PMID- 19474902 TI - Trapping and mixing of particles in water using a microbubble attached to an NSOM fiber probe. AB - Low power cw laser radiation at lambda=1.32microm was coupled into a chemically etched,metalized Near-Field Scanning Optical Microscopy (NSOM) fiber probe to generate a stable microbubble in water as well as in other fluids.The microbubble,which was attached to the end face of the fiber probe,was used to trap, manipulate and mix micron sized glass,latex and fluorescent particles as well as biological material. PMID- 19474903 TI - Measurement of anomalous dispersion in microstructured fibers using spectral modulation. AB - We report on a simple technique to measure the anomalous dispersion of small-core microstructured fibers using short optical pulses. The method relies on the spectral modulation resulting from the evolution of the input pulse into a propagating soliton wave. The technique allows for a direct measurement of the dispersion at the desired wavelength from a single pulse. The measurement error is estimated to be less than 10%. PMID- 19474904 TI - Gaussian pulsed beams with arbitrary speed. AB - It is shown that the homogeneous scalar wave equation under a generalized paraxial approximation admits of Gaussian beam solutions that can propagate with an arbitrary speed, either subluminal or superluminal, in free-space. In suitable moving inertial reference frames, such solutions correspond either to standard stationary Gaussian beams or to "temporal" diffracting Gaussian fields. PMID- 19474905 TI - Dispersion properties of square-lattice photonic crystal fibers. AB - In this paper the guiding properties of photonic crystal fibers with a square lattice of air-holes in a silica matrix have been studied for the first time. The dispersion curves of fibers with different hole-to-hole spacing and air-hole diameter have been accurately calculated. Negative values of the dispersion parameter and the dispersion slope have been obtained with a hole-to-hole spacing of 1 microm. A comparison between fibers with square and triangular lattice has been also performed, taking into account the dispersion properties and the effective area in the wavelength range between 1200 nm and 1600 nm. PMID- 19474907 TI - Polarization maintaining large mode area photonic crystal fiber. AB - We report on a polarization maintaining large mode area photonic crystal fiber. Unlike, previous work on polarization maintaining photonic crystal fibers, birefringence is introduced using stress applying parts. This has allowed us to realize fibers, which are both single mode at any wavelength and have a practically constant birefringence for any wavelength. The fibers presented in this work have mode field diameters from about 4 to 6.5 micron, and exhibit a typical birefringence of 1.510(-4). PMID- 19474906 TI - Hyperspectral imaging of gases with a continuous-wave pump-enhanced optical parametric oscillator. AB - We demonstrate a system for the active real-time hyperspectral imaging of gases using a combination of a compact, pump-enhanced, continuous-wave optical parametric oscillator as an all-solid-state mid-infrared source of coherent radiation and an electro-mechanical polygonal imager. The wide spectral coverage and high spectral resolution characteristics of this source means that the system is capable of being selectively tuned into the absorption features of a wide variety of gaseous species. As an example we show how the largest absorption coefficient exhibited by methane at 3057.7cm(-1) can be accessed (amongst others) and gas plumes imaged in concentrations as low as 30ppm.m using a parametric oscillator based on periodically-poled RbTiOAsO(4) (PP-RTA). PMID- 19474908 TI - Modeling of PCF with multiple reciprocity boundary element method. AB - The multiple reciprocity boundary element method (MRBEM) is applied to the modeling of Photonic Crystal Fiber (PCF). With the MRBEM, the Helmholtz equation is converted into an integral equation using a series of higher order fundamental solutions of the Laplace equation. It is a much more efficient method to analyze the dispersion, birefringence and nonlinearity properties of PCFs compared with the conventional direct boundary element method (BEM). PMID- 19474909 TI - Cylindrical vector beam focusing through a dielectric interface: comment. AB - Errors in the results and conclusions presented in the paper "Cylindrical vector beam focusing through a dielectric interface" by Biss and Brown (Opt. Express 9, 490-497 (2001)) are discussed. PMID- 19474910 TI - Cylindrical vector beam focusing through a dielectric interface: reply to comment. AB - A reply to the comment by van de Nes et al. directed to the paper of "Cylindrical vector beam focusing through a dielectric interface," by Biss and Brown, Opt. Express, 9 490-497, (2001). PMID- 19474911 TI - Dopant diffusion during optical fibre drawing. AB - Diffusion of Ge and F was studied during drawing of silica optical fibres. Preforms were drawn using various draw conditions and fibres analysed using the etching and Atomic Force Microscope (AFM) technique. The results were confirmed by comparison with fibre Refractive Index Profiles (RIP). Both Ge and F were found to diffuse at high temperature, 2100 degrees C, and low draw speed, 10m/min. Diffusion simulations showed that most diffusion occurred in the neck down region. The draw temperature and preform feed rate had a comparable effect on diffusion, whereas preform diameter did not significantly affect the diffusion. PMID- 19474912 TI - Two-stage design method for realization of photonic bandgap structures with desired symmetries by interference lithography. AB - Interference lithography for the fabrication of photonic crystals is considered. A two-stage design method for realization of photonic bandgap structures with desired symmetries is developed. An optimal photonic crystal with a large bandgap is searched by adjusting some parameters while keeping some basic symmetry of the unit cell unchanged. A nonlinear programming method is then used to find the optimal electric field vectors of the laser beams and realize the desired interference pattern. The present method is useful for a rational and systematical design of new photonic bandgap structures. PMID- 19474913 TI - Exposure-schedule study of uniform diffraction efficiency for DSSM holographic storage. AB - An exposure-schedule theory of uniform diffraction efficiency for a Dynamic Static speckle multiplexing (DSSM) volume holographic storage system is proposed. The overlap-factor (? overlap) is introduced into the system to compensate for the erasure effect of the static speckle multiplexing scheme. The exposure schedule which is an inverse recursion formula is determined. Experimental results are obtained in a LiNbO(3):Fe crystal and 400 holograms with uniform diffraction efficiency are achieved by the use of the new exposure-schedule. PMID- 19474914 TI - Production of quasi-crystal template patterns using a dual beam multiple exposure technique. AB - We present a dual beam multiple exposure technique that can generate complex 2-D quasi-crystal template structures. The optical system is based on the interference of two laser beams producing a family of high intensity planes. Controlled reorientation of a photosensitive sample between exposures results in an exposure dose, when developed, returns a quasi-crystal pattern. Results are shown in which quasi-crystal patterns with 8, 10, and 12-fold rotation symmetry are produced in photoresist. The results of several test runs are shown in which the quasi-crystal patterns developed in photoresist are subsequently etched into silicon. Based on an extended application of the dual beam multiple exposure optical system, a potential technique for producing 3-D quasi-crystal patterns is presented. PMID- 19474915 TI - Resonantly enhanced transmission of terahertz radiation through a periodic array of subwavelength apertures. AB - We demonstrate resonantly enhanced transmission of freely propagating coherent terahertz radiation through free-standing metal foils perforated with periodic arrays of sub-wavelength apertures. These arrays consist of 400 microm diameter apertures periodically spaced by 1 mm and 600 microm diameter apertures periodically spaced by 1.5 mm. We measure absolute amplitude transmission coefficients of ~0.6 at the resonance wavelength. Correspondingly, the ratio of the absolute amplitude transmission coefficient to the fractional aperture area at these resonance frequencies is ~5. This value at terahertz frequencies is significantly larger than equivalent values measured at optical frequencies. PMID- 19474916 TI - Simulations and experiments on self-focusing conditions in nematic liquid-crystal planar cells. AB - Owing to the nonlinear effect of optical field-induced director reorientation, self-focusing of an optical beam can occur in nematic liquid crystals and an almost diffraction-compensated propagation can be observed with milliwatts of light power and propagation lengths of several millimeters. This opens the way for applications in all-optical signal handling and reconfigurable optical interconnections. Self-focusing of an optical beam in nematic liquid-crystal cells has been studied experimentally and by means of numerical simulation. The relationships between bias voltage, cell thickness and required optical power have been examined, thus allowing the determination of the most favorable conditions for soliton-like beam propagation. PMID- 19474917 TI - Transient regime in a nth-order cascaded CW Raman fiber laser. AB - The transient regime of a nth-order CW Raman fiber laser is simulated from switch on to the steady-state and from the steady-state to switch-off. The Stokes waves exhibit high-power spikes during the switch-on transition. We find that the high order Stokes fields reach steady-state faster than the low order ones and the pump. PMID- 19474918 TI - Single-mode guiding properties of subwavelength-diameter silica and silicon wire waveguides. AB - Single-mode optical wave guiding properties of silica and silicon subwavelength diameter wires are studied with exact solutions of Maxwell's equations. Single mode conditions, modal fields, power distribution, group velocities and waveguide dispersions are studied. It shows that air-clad subwavelength-diameter wires have interesting properties such as tight-confinement ability, enhanced evanescent fields and large waveguide dispersions that are very promising for developing future microphotonic devices with subwavelength-width structures. PMID- 19474919 TI - Refractive index profile of fused-fiber couplers cross-section. AB - We investigate the refractive index profile of the cross-section of fused type fiber-optic couplers by solving the convective diffusion equation. We assume the refractive index to be a linear function of the dopant concentration. The viscous sintering of the optical fibers is considered as the motion of an incompressible Newtonian fluid which is driven by the surface tension acting at the free boundary. The internal velocity field is obtained using conformal mapping methods. We present numerical solutions of the resulting equations and compare them with experimental observations. PMID- 19474920 TI - Supercontinuum generation in a photonic crystal fiber with two zero dispersion wavelengths. AB - We demonstrate supercontinuum generation in a highly nonlinear photonic crystal fiber with two closely lying zero dispersion wavelengths. The special dispersion of the fiber has a profound influence on the supercontinuum which is generated through self-phase modulation and phasematched four-wave mixing and not soliton fission as in the initial photonic crystal fibers. The supercontinuum has high spectral density and is extremely independent of the input pulse over a wide range of input pulse parameters. Simulations show that the supercontinuum can be compressed to ultrashort pulses. PMID- 19474921 TI - Characterization of surface crystallization in Ge-doped graded-index silica glass. AB - Surface crystallization was induced in Ge-doped silica glass samples from a graded-index optical fiber preform by re-heating them at 1100 degrees C for several hours. X-ray diffraction and second-harmonic generation (SHG) microscopy have been utilized to investigate the crystalline phases formed. Experimental results indicate that the predominant crystalline phase is alpha-cristobalite. The cross-sectional distribution of the crystal particles has also been measured with the SHG microscopy and the result is in good agreement with that from traditional bright field light microscopy. PMID- 19474922 TI - Multiphoton intrapulse interference 6; binary phase shaping. AB - We demonstrate a new approach to laser control using binary phase shaping. We apply this method to the problem of spectrally narrowing multiphoton excitation using shaped laser pulses as required for selectivity in two-photon microscopy. The symmetry of the problem is analyzed from first principles and a rational solution is proposed. Successful experimental implementation and simulations are presented using 10 fs ultrashort pulses. The proposed solution is a factor of 6 better than the sinusoidal phase used previously by our group. An evolutionary learning algorithm was used to efficiently improve the solution by a further factor of 2.5 because of the greatly reduced search space afforded by binary phase shaping. PMID- 19474923 TI - High-quality integral videography using a multiprojector. AB - Integral videography (IV) is an animated extension of integral photography. Despite IV's many advantages, the quality of its spatial images has thus far been poor; the pixel pitch of the display and the lens pitch are considered to be the main factors affecting the IV image format. Our solution for increasing pixel density is to use multiple projectors to create a high-resolution image and project the resultant image onto a small screen by using long-zoom-lens projection optics. We manufactured a lens array for the display device, and here we present experimental results on using two SXGA projectors. The pixel pitch and lens pitch of the new display are 85 mum and 1.016 mm, respectively. The multiprojector IV display device has a spatial resolution of approximately 1, 2, and 3 mm for image depths of 10, 35, and 60 mm, respectively, in front of and behind the lens array. PMID- 19474924 TI - Three-dimensional projection integral imaging using micro-convex-mirror arrays. AB - Three-dimensional projection integral imaging using micro-convex-mirror arrays is presented. In this scheme, a pseudoscopic to orthoscopic image conversion process is not required even if elemental images of direct camera pickup are used. In addition, a wide viewing angle without image flipping can be achieved even if optical barriers are not used. The feasibility of the proposed scheme was experimentally demonstrated, in which the viewing angle of more than 60 degrees was obtained. To the best of our knowledge, this is the largest viewing angle demonstrated by a single integral imaging system. PMID- 19474925 TI - Two-dimensional wavelength demultiplexing employing multilevel arrayed waveguides. AB - Two-dimensional (2D) optical wavelength demultiplexing is demonstrated by employing multilevel arrayed waveguides as a 2D diffraction grating, named the 2D arrayed waveguide grating (2D-AWG). Since the monochromatic lightwave is diffracted by the 2D-AWG to a series of periodic spots with 2D diffraction orders in both x and y directions while the dispersion direction is never parallel to the x or y direction, we can obtain 2D wavelength demultiplexing exploiting diffraction orders of either the x or y direction. One of the two dispersion components is designed much larger than the other, and the correspondent spatial free spectral range component is set properly to ensure high diffraction efficiency. The input and output ports can also be designed based on the multilevel lightwave circuit (MLC), and their level planes can be tuned parallel to that of the MLC-based 2D-AWG, which makes it feasible to integrate the 2D-AWG with the input port and/or the output port. It provides a promising way to realize large-scale and high-density optical multiplexers/demultiplexers. PMID- 19474926 TI - Low propagation loss of 0.76 dB/mm in GaAs-based single-line-defect two dimensional photonic crystal slab waveguides up to 1 cm in length. AB - Straight single-line-defect photonic crystal (PC) waveguides on GaAs slabs with lengths of 1, 4, and 10 mm have been fabricated. By controlling the Al content of a sacrificial AlGaAs clad layer and the wet etching duration, a PC core layer with a very smooth surface was obtained. Atomic force microscope images indicate that the roughness on the top surface is less than 1 nm. An extremely low propagation loss of 0.76 dB/mm for the GaAs-based PC waveguide was achieved. PMID- 19474928 TI - Compact measurement of low-PMD optical telecommunication fibers. AB - Accurate polarization mode dispersion (PMD) measurements on modern telecommunication fiber involve significant fiber layout and handling problems. These problems severely limit the quality and quantity of data that can be taken. A new method is proposed for measuring PMD using a large diameter collapsible spool with localized external perturbation (LEP). This method allows the necessary repeated measurements, and virtually eliminates environmental effects, which complicate measurements of low-PMD modern fibers. It is shown that the method produces nearly identical PMD results to a more laborious, conventional method. PMID- 19474927 TI - Equifrequency surfaces in a two-dimensional GaN-based photonic crystal. AB - We established the angular conditions that maintain the quasi-phase matching conditions for enhanced second-harmonic generation. To do that, we investigated the equifrequency surfaces of the resonant Bloch modes of a two-dimensional periodic, hole-array photonic crystal etched into a GaN/sapphire epitaxial structure. The equifrequency surfaces exhibit remarkable shapes, in contrast to the simpler surfaces of a one-dimensional structure. The observed anisotropy agrees well with the surfaces calculated by a scattering matrix method. The equifrequency surfaces at fundamental and second-harmonic frequencies provide the values of polar and azimuthal angles that maintain quasi-phase matching conditions for enhanced second-harmonic generation over an extended tuning range. The predicted values for quasi phase-matching conditions show that frequency tuning for the two-dimensional case covers an about two times larger fractional bandwidth relative to the one-dimensional case. PMID- 19474929 TI - Dual wavelength demultiplexing by coupling and decoupling of photonic crystal waveguides. AB - We demonstrate that the fundamental mode of the two coupled photonic crystal waveguides (PCWs) can be odd parity in a triangular photonic crystal and their dispersion curves do intersect. Thus, the PCWs are decoupled at the crossing point. By employing the decoupling at the crossing-point frequency and ultra short coupling length for another frequency, we designed a dual-wavelength demultiplexer with a coupling length of only two wavelengths and output power ratio as high as 15 dB. A loop-shape PCW is adapted to eliminate the backward energy flow. PMID- 19474930 TI - Full-vectorial analysis of complex refractive index photonic crystal fibers. AB - We investigated the modal properties of complex refractive-index core photonic crystal fibers (PCFs) with the supercell model. The validity of the approach is shown when we compare our results with those reported earlier on a step complex refractive-index profile. The imaginary part of the electric field results in wave-front distortion in the complex refractive-index profile PCFs, which means that the power flows out or into the doped region according to the sign of the imaginary part of the refractive index. A simple formula is proposed for calculating the gain or loss coefficients of these fibers. The numerical results obtained by the approximation formula agree well with the full-vectorial results. PMID- 19474931 TI - Time efficient Chinese remainder theorem algorithm for full-field fringe phase analysis in multi-wavelength interferometry. AB - We present a computationally efficient method for solving the method of excess fractions used in multi-frequency interferometry for absolute phase measurement. The Chinese remainder theorem, an algorithm from number theory is used to provide a unique solution for absolute distance via a set of congruence's based on modulo arithmetic. We describe a modified version of this theorem to overcome its sensitivity to phase measurement noise. A comparison with the method of excess fractions has been performed to assess the performance of the algorithm and processing speed achieved. Experimental data has been obtained via a full-field fringe projection system for three projected fringe frequencies and processed using the modified Chinese remainder theorem algorithm. PMID- 19474932 TI - Microoptomechanical pumps assembled and driven by holographic optical vortex arrays. AB - Beams of light with helical wavefronts can be focused into ring-like optical traps known as optical vortices. The orbital angular momentum carried by photons in helical modes can be transferred to trapped mesoscopic objects and thereby coupled to a surrounding fluid. We demonstrate that arrays of optical vortices created with the holographic optical tweezer technique can assemble colloidal spheres into dynamically reconfigurable microoptomechanical pumps assembled by optical gradient forces and actuated by photon orbital angular momentum. PMID- 19474933 TI - Modal power loss coefficients for highly overmoded rectangular dielectric waveguides based on free space modes. AB - A simple formalism to estimate modal power loss coefficients for an overmoded rectangular waveguide with rough surfaces is presented. The method is based on small index differences where the true radiation modes are approximated by free space modes. Loss coefficients are important in order to establish more accurate channel models for, e.g., optical backplane communication systems. The theory is validated by comparing the loss coefficients of a squeezed rectangular waveguide with the loss coefficients of a slab waveguide. PMID- 19474934 TI - Comparisons of the transmitted signals of time, aperture, and angle gating in biological tissues and a phantom. AB - We measure transmitted signals with time, aperture, and angle gating for comparison in micro-sphere suspension, chicken breast and chicken liver tissues. We find that in each sample, the small aperture-gated (angle-gated) signals for imaging are essentially different from those of early time gating. Meanwhile, the signals obtained from aperture and angle gating come from quite different parts of the transmitted photons. For biological tissues of different structures, different gating methods may lead to different levels of imaging quality. Also, the results indicate the generally different scattering characteristics of biological tissues from that of a particle-based phantom. The scattering nature in the biological tissues may imply that random continuum scattering needs to be considered in biological imaging. Between chicken breast and liver tissues, the time-gated data show that the later has stronger scattering and absorption. PMID- 19474935 TI - Ultrashort pulse characterisation with SHG collinear-FROG. AB - We outline criteria for fast and accurate acquisition of collinear FROG (CFROG) trace and how it can be transformed into the more traditional noncollinear FROG trace. The CFROG has an intrinsically simple geometry that provides greater versatility as well as the ability for built-in delay calibration and enhanced error-checking. The procedure, based on data processing, allows conventional SHG FROG retrieval algorithms to be used. This technique is tested numerically and experimentally giving excellent results. This work represents an attractive alternative to the traditional, more complex non-collinear FROG technique while, at the same time, extending its use to experiments where collinear geometry is imposed. PMID- 19474936 TI - Torque-generating malaria-infected red blood cells in an optical trap. AB - We have used optical tweezers to trap normal and Plasmodiuminfected red blood cells (iRBCs). Two different facets of the behavior of RBCs in infrared light fields emerge from our experiments. Firstly, while the optical field modifies both types of RBCs in the same fashion, by folding the original biconcave disk into a rod-like shape, iRBCs rotate with linearly polarized light whereas normal RBCs do not. Secondly, and in the context of known molecular motors, our measurements indicate that the torque of rotating iRBCs is up to three orders of magnitude larger. PMID- 19474937 TI - Generation of a broadband spectral comb with multiwave mixing by exchange of an impulsively stimulated phonon. AB - A broadband spectral comb is generated around the third harmonics of incident light with the nondegenerate, impulsively stimulated Raman scattering technique using ultrashort light pulses. The comb has a spectral width of more than 4000 cm(-1), and its envelope becomes smooth as the light powers are increased. It consists of discrete lines, the spacing of which is equal to the frequency of the Raman-active phonon mode, even though the frequency of the phonon mode is far smaller than the frequency difference between the two incident light pulses. The multiline structure is generated with multiwave mixing by exchange of the impulsively stimulated phonon among the signals. PMID- 19474938 TI - Phase measurement for segmented optics with 1D diffraction patterns. AB - A simple approach for measuring the piston error between two adjacent segments in a primary mirror of a telescope, based on the one dimension analysis of the diffraction pattern produced by a divided slit, is proposed. Using two wavelengths allows an increase of the dynamic range of the measurement. The main advantages are that even maintaining the correlation based scheme used by other authors, the time of processing should be reduced. Some experimental results are presented which show that for one wavelength a precision of 3 nm and a dynamic range of 316 nm are feasible for the red line of a He-Ne laser. For the two wavelength experiments a precision of 53 nm is obtained for lambda(eq)/2 = 1670 nm dynamic range. PMID- 19474939 TI - Characterization protocol to evaluate chiral smectic liquid crystals for high-end display applications. AB - A protocol based on systematic experimental measurements to characterize the electro-optic behavior of chiral smectic liquid-crystal (LC) materials with V/W shaped responses is presented. An experimental smectic LC material has been checked by use of this protocol. It has been found that results derived from this procedure permit a reasonable evaluation of the electro-optic performance of these LC materials as well as their capability to be used in high-end display applications. PMID- 19474940 TI - Photonic nanojet enhancement of backscattering of light by nanoparticles: a potential novel visible-light ultramicroscopy technique. AB - We report what we believe to be the first evidence of localized nanoscale photonic jets generated at the shadow-side surfaces of micronscale, circular dielectric cylinders illuminated by a plane wave. These photonic nanojets have waists smaller than the diffraction limit and propagate over several optical wavelengths without significant diffraction. We have found that such nanojets can enhance the backscattering of visible light by nanometer-scale dielectric particles located within the nanojets by several orders of magnitude. Not involving evanescent fields and not requiring mechanical scanning, photonic nanojets may provide a new means to detect and image nanoparticles of size well below the diffraction limit. This could yield a potential novel ultramicroscopy technique using visible light for detecting proteins, viral particles, and even single molecules; and monitoring molecular synthesis and aggregation processes of importance in many areas of biology, chemistry, material sciences, and tissue engineering. PMID- 19474941 TI - Variable optical attenuator based on polymer stabilized twisted nematic liquid crystal. AB - A variable optical attenuator (VOA) based on polymer stabilized twisted nematic (PSTN) liquid crystal (LC) is demonstrated. Comparing with the normal twisted nematic LC-based VOA, PSTN exhibits a much faster response time. Moreover, the polymer networks effectively eliminate the backflow effect which exists in the normal TNLC cell. The attenuation mechanism of the PSTN LC was studied. Both polarization rotation and light scattering effects are found to contribute to the optical attenuation. The ratio between these two mechanisms can be adjusted by changing the polymer concentration and polymer network domain size. PMID- 19474942 TI - Nano dispersion amplified waveguide structures. AB - A highly dispersive waveguide structure is proposed tocefficiently compress and expand ultra short pulses in a package forming a sufficiently small footprint. A sub-wavelength grating is fashioned into a ridge waveguide to take advantage of multiple dispersive effects and spread the mode over a significantly larger area than a standard single-mode waveguide. The structure is designed to take advantage of the amplified dispersion near cutoff. Modal analysis is performed on two variations of the structure using a finite element solver package. The predicted dispersion is sufficient to double the width of a 1 ps pulse within the width of a standard 5 inch (127 mm) wafer. A theoretical analysis of the grating component composing the structure confirms that the dispersion values are fully reasonable. PMID- 19474943 TI - Liquid crystal blazed gratings formed in a single-step through photo-induced localization of polymer into a prismatic structure. AB - A liquid crystal blazed grating having a prismatic polymer microstructure has been developed. The polymer structure is fabricated by photo-induced localization and polymerization of a small concentration of monomer onto one substrate of an electro-optical cell by using ultraviolet light irradiation at the direction 45 degrees from normal incident. Using this method a periodical one-dimensional pattern with a prismatic shape of polymer can be formed on a one-dimensional pattern-forming state of a cholesteric host. The optical diffraction properties of the grating are evaluated by the application of electric field and light incident angles. PMID- 19474944 TI - Efficient phase conjugation by pico-second four-wave-mixing in solid-dye amplifier. AB - We demonstrate 2.5 times phase conjugation by four-wave-mixing with the use of pico-second pulses in a rhodamine6G dye polymer amplifier. Phase conjugation pulse shortening by a factor of 2 is also measured. PMID- 19474945 TI - Coherent DIAL profiling in turbulent atmosphere. AB - Because of the presence of atmospheric refractive turbulence, it is necessary to use simulations of beam propagation to examine the uncertainty added to the differential absorption lidar (DIAL) measurement process of a practical heterodyne lidar. The outcomes of our analysis illustrate the relative sensitivity of coherent DIAL systems under general atmospheric conditions and different instrument configurations. PMID- 19474946 TI - Secure information display with limited viewing zone by use of multi-color visual cryptography. AB - We propose a display technique that ensures security of visual information by use of visual cryptography. A displayed image appears as a completely random pattern unless viewed through a decoding mask. The display has a limited viewing zone with the decoding mask. We have developed a multi-color encryption code set. Eight colors are represented in combinations of a displayed image composed of red, green, blue, and black subpixels and a decoding mask composed of transparent and opaque subpixels. Furthermore, we have demonstrated secure information display by use of an LCD panel. PMID- 19474947 TI - Clustering of Mueller matrix images for skeletonized structure detection. AB - This paper extends and refines previous work on clustering of polarization encoded images. The polarization-encoded images used in this work are considered as multidimensional parametric images where a clustering scheme based on Markovian Bayesian inference is applied. Hidden Markov Chains Model (HMCM) and Hidden Hierarchical Markovian Model (HHMM) show to handle effectively Mueller images and give very good results for biological tissues (vegetal leaves). Pretreatments attempting to reduce the image dimensionality based on the Principal Component Analysis (PCA) turns out to be useless for Mueller matrix images. PMID- 19474948 TI - Calculation of the vectorial field distribution in a stratified focal region of a high numerical aperture imaging system. AB - We present an algorithm for calculating the field distribution in the focal region of stratified media which is fast and easy to implement. Using this algorithm we study the effect on the electric field distribution of an air gap separating a solid immersion lens and a sample, where we analyse the maximum distance for out-of-contact operation. Also, we study how the presence of a metallic substrate affects the field distribution in the focal region; the interference effects of the reflected field could be used as an alternative for 4Pi-microscopy. PMID- 19474949 TI - Realization of refractive microoptics through grayscale lithographic patterning of photosensitive hybrid glass. AB - Refractive microlenses with more than 50 microm sag are fabricated using grayscale lithography. Mechanical assembly features are made simultaneously alongside the microlenses to facilitate high precision assembly of miniature optical systems. The microlens elements are formed using lithographic patterning of photosensitive hybrid sol-gel glass requiring no etch transfer to the substrate material. Grayscale lithography enables the straightforward patterning of aspheric lenses and arbitrary surfaces within the material depth. Lessons learned in the design of a grayscale photomask are described. Characterization of the fabricated lens elements is reported including lens shape, surface quality, and image quality of a complete assembled imaging system. PMID- 19474950 TI - Engineering the filter response of photonic crystal microcavity filters. AB - Compact photonic crystal (PhC) filters will play a vital role in wavelength division multiplexing applications and they could be the stepping stones towards the realisation of dense and multifunctional photonic integrated circuits. Bragg grating concepts are applied to PhC filters to control their response by introducing suitable phase shifts and choosing appropriate locations and magnitudes. Moreover, the variation of the PhC hole size at the input and output regions could offer an extra degree of freedom in tailoring the filter characteristics. The ability to engineer and control the filter response of photonic crystal filters is investigated in this paper. PMID- 19474951 TI - Low-nonlinearity single-transverse-mode ytterbium-doped photonic crystal fiber amplifier. AB - We report on an air-clad large-core single-transverse-mode ytterbium-doped photonic crystal fiber with a mode-field-diameter of 35 microm, corresponding to a mode-field-area of ~1000 microm(2). In a first experiment this fiber is used to amplify 10-ps pulses to a peak power of 60 kW without significant spectral broadening due to self-phase modulation allowing for the frequency up-conversion of these pulses using narrow-bandwidth phase matched nonlinear crystals. PMID- 19474952 TI - Crucial effects of the anisotropy on optical field induced pattern formation in nematic liquid crystal films. AB - We present here the crucial effects of material anisotropy on optical field induced pattern formation in the one-feedback-mirror arrangement which utilizes the nematic liquid crystal film as the nonlinear medium. By using the quasi static electric-field-biased planar-aligned homogeneous nematic liquid crystal (NLC) films, we observe both the hexagon and the roll patterns which can be switched optically due to the intrinsic anisotropic distribution of the threshold intensity. The anisotropy comes from the anisotropic nonlinear response of the NLC film and is the crucial factor for such a one-feedback-mirror system to form both the roll and hexagon patterns. The observed phenomena can be explained from the linear stability analysis of the governing diffusion-like equation. The experimental results indicate that the stable roll patterns are formed at low input light power and the stable hexagon patterns formed at high input power. PMID- 19474953 TI - Reliability of laser safety eye wear in the femtosecond regime. AB - Appropriate eye protection is a prerequisite for the safe operation of ultrashort laser systems in industrial and laboratory environments. In this paper we report on the measurement of the transmission of ion-doped phosphate glass filters for pulses having a center wavelength of 800nm, a duration of 10fs to 1.2ps and a fluence range of 0.01 to 30J/cm(2). The measurements suggest, that the filter material preserves its protective features over the whole range. Saturation of absorption was only observed in the picosecond pulse duration range. PMID- 19474954 TI - Bandwidth dependence of the heterodyne efficiency in low coherence interferometry. AB - The effect of radiation bandwidth on the heterodyne detection process is discussed. We show that, although neglected in current formalisms, the spectral changes induced by the scattering process are decreasing the heterodyne detection efficiency. This effect depends on the bandwidth of the radiation used. PMID- 19474955 TI - Broad band and low loss mid-IR flexible hollow waveguides. AB - This paper introduces a deposition method to create a multilayered waveguide with alternating layers of high index of refraction contrast. A very thin Ag layer, practically transparent in the mid-IR radiation wavelengths of CO(2) and Er-YAG lasers, was created. This enabled a good contrast of the indices of refraction of silver/silver iodide. Theoretical calculations as well as experiments have shown that transmission was higher at these wavelengths for two pair layers, in comparison to one pair of silver/silver iodide. Windows of transmittance and small sensitivity to bending were demonstrated for those two pair layer waveguides. This method could be extended to an increased number of pairs to configure a true photonic band gap waveguide. PMID- 19474956 TI - Dispersion-cancelled and dispersion-sensitive quantum optical coherence tomography. AB - Quantum optical coherence tomography (QOCT) makes use of an entangled twin-photon light source to carry out axial optical sectioning. We have probed the longitudinal structure of a sample comprising multiple surfaces in a dispersion cancelled manner while simultaneously measuring the group-velocity dispersion of the interstitial media between the reflecting surfaces. The results of the QOCT experiments are compared with those obtained from conventional optical coherence tomography (OCT). PMID- 19474957 TI - Resonator based measurement technique for quantification of minute birefringence. AB - We present a new method for quantification of minute birefringence in high finesse resonators. The method is based on observing the homodyne polarization mode beat at the output of the resonator. We show that the mode beat is generated by a phase mismatch of a polarization mode in the cavity and that the magnitude of the birefringence is proportional to the beat frequency. We demonstrate the sensitivity of the technique by measuring polarization properties of a twisted 0.275 m long single-mode fiber cavity. Maximum beat length of the fiber was found to be 10.6 m, which is almost 40 times longer than the length of the studied fiber. PMID- 19474958 TI - Low-loss photonic crystal fibers for transmission systems and their dispersion properties. AB - We report on a single-mode photonic crystal fiber with attenuation and effective area at 1550 nm of 0.48 dB/km and 130 microm(2), respectively. This is, to our knowledge, the lowest loss reported for a PCF not made from VAD prepared silica and at the same time the largest effective area for a low-loss (< 1 dB/km) PCF. We briefly discuss the future applications of PCFs for data transmission and show for the first time, both numerically and experimentally, how the group velocity dispersion is related to the mode field diameter. PMID- 19474959 TI - Nanosecond Z-scan measurements of the nonlinear refractive index of fused silica. AB - We present the results of Z-scan studies carried out on fused silica at 1064nm and 532nm with two different nanosecond pulse durations. Such measurements in silica and in the nanosecond regime are possible thanks to a high sensitivity setting up of the Z-scan method and in-situ characterizations of the spatio temporal parameters of the beam. Besides, with the use of a newly adapted numerical simulation only the calibration errors of the measurement devices are significant. In these conditions, we found a higher value of the nonlinear refractive index than in the femtosecond regime and we show that these values depend on pulse duration, which indicates the contribution of nanosecond mechanisms like electrostriction. PMID- 19474960 TI - High-energy, high-contrast, double-confocal multipass amplifier. AB - We have developed a high-contrast, high-beam-quality Ti:sapphire amplifier producing pulses of 10 mJ in a single stage with 19% efficiency. The amplifier has a double-confocal multipass ring configuration that allows for a large mode volume by use of a collimated beam in the gain medium. We have designed the amplifier optics to correct for aberrations and for spatial gain narrowing. The compressed output beam has an M(2) of 1.15. The use of an internal saturable absorber in the amplifier results in an intensity contrast of ~10(9). We anticipate this design will be useful to extend the multipass architecture to low gain media and to still higher output energy. PMID- 19474961 TI - Simple and sensitive method for visual detection of temporal asymmetry of ultrashort laser pulses. AB - A simple method is presented for visual detection of pulse asymmetry in ultrashort laser pulses, based on an unbalanced modified spectrum auto interferometric correlation. It may be experimentally realized using a second order interferometric autocorrelator coupled with a fast data analysis computer program or electronic hardware. This method should permit real time visual detection of a very small amount of pulse asymmetry without any "direction of time" ambiguity, with a much higher sensitivity compared to unbalanced third order correlation. PMID- 19474962 TI - Compact finite-difference frequency-domain method for the analysis of two dimensional photonic crystals. AB - A finite-difference frequency-domain method based on the Yee's cell is utilized to analyze the band diagrams of two-dimensional photonic crystals with square or triangular lattice. The differential operator is replaced by the compact scheme and the index average scheme is introduced to deal with the curved dielectric interfaces in the unit cell. For the triangular lattice, the hexagonal unit cell is converted into a rectangular one for easier mesh generation. The band diagrams for both square and triangular lattices are obtained and the numerical convergence of computed eigen frequencies is examined and compared with other methods. PMID- 19474963 TI - Use of a simple cavity geometry for low and high repetition rate modelocked Ti:sapphire lasers. AB - We demonstrate a general procedure for varying the repetition rate of a modelocked Ti:sapphire laser using an asymmetric focusing geometry. Using this procedure, we have made an extended length cavity with a repetition rate of 45 MHz, and a reduced length cavity with a repetition rate of 275 MHz, each of which generates sub-20 fs pulses. This procedure allows the repetition rate of the laser to be more precisely tailored for a variety of applications without compromise in performance. PMID- 19474964 TI - Real-time interactive optical micromanipulation of a mixture of high-and low index particles. AB - We demonstrate real-time interactive optical micromanipulation of a colloidal mixture consisting of particles with both lower (n(L) < n(0)) and higher (n(H)> n(0)) refractive indices than that of the suspending medium (n(0)). Spherical high- and low-index particles are trapped in the transverse plane by an array of confining optical potentials created by trapping beams with top-hat and annular cross-sectional intensity profiles, respectively. The applied method offers extensive reconfigurability in the spatial distribution and individual geometry of the optical traps. We experimentallydemonstrate this unique feature by simultaneously trapping and independently manipulating various sizes of spherical soda lime micro -shells (n(L) >> 1.2) and polystyrene micro-beads (n(H) = 1.57) suspended in water (n(0) = 1.33). PMID- 19474965 TI - Thermal lens shaping in Brewster gain media: A high-power, diode-pumped Nd:GdVO(4) laser. AB - A straightforward method is presented for generating a stigmatic spherical thermal lens in laser-diode-pumped, Brewster-cut solid-state gain media by shaping the aspect ratio of the elliptical pumped region. Demonstration of this laser head design with Nd:GdVO(4) as the gain medium yields a stable, efficient, high-power (>20W) diode-pumped laser at 1063nm. Analysis of the spatial mode characteristics of a 67cm-long symmetric resonator both confirms the radially symmetric nature of the pump-induced thermal lens and indicates that laser resonators incorporating this head design can readily generate a high spatial beam quality (M(2) < 2). PMID- 19474966 TI - Microring-resonator-based add-drop filters in SiN: fabrication and analysis. AB - Third-order add-drop filters based on series-coupled microring resonators were fabricated in silicon-rich silicon nitride with accurate dimensional control and negligible sidewall roughness. For the first time, a low 3 dB drop loss is demonstrated with a wide 24 nm free-spectral-range in a high-order microring filter without using the Vernier effect. The spectral response is matched by rigorous numerical simulation, and non-idealities in the drop- and through-port responses are shown to be of design origin and to be correctable. PMID- 19474967 TI - Gas visualization of industrial hydrocarbon emissions. AB - Gases leaking from a polyethene plant and a cracker plant were visualized with the gas-correlation imaging technique. Ethene escaping from flares due to incomplete or erratic combustion was monitored. A leakage at a high-pressure reactor tank could be found and visualized by scanning the camera system over the industrial site. The image processing methods rely on the information from three simultaneously captured images. A direct and a gas-filtered infrared image are recorded with a split-mirror telescope through a joint band-pass filter. The resulting path-integrated gas concentration image, derived from the two infrared images, is combined with a visible image of the scene. The gas-correlation technique also has the potential to estimate the flux in the gas plume by combining a wind vector map, derived by cross-correlating the images in time, with a calibrated gas path-integrated concentration image. The principles of the technique are outlined and its potential discussed. PMID- 19474968 TI - Refractive index profiles of Ge-doped optical fibers with nanometer spatial resolution using atomic force microscopy. AB - We show a quantitative connection between Refractive Index Profiles (RIP) and measurements made by an Atomic Force Microscope (AFM). Germanium doped fibers were chemically etched in hydrofluoric acid solution (HF) and the wet etching characteristics of germanium were studied using an AFM. The AFM profiles were compared to both a concentration profile of the preform determined using a Scanning Electron Microscope (SEM) and a RIP of the fiber measured using a commercial profiling instrument, and were found to be in excellent agreement. It is now possible to calculate the RIP of a germanium doped fiber directly from an AFM profile. PMID- 19474969 TI - Fabrication-tolerant high quality factor photonic crystal microcavities. AB - A two-dimensional photonic crystal microcavity design supporting a wavelength scale volume resonant mode with a calculated quality factor (Q) insensitive to deviations in the cavity geometry at the level of Q~2x10(4) is presented. The robustness of the cavity design is confirmed by optical fiber-based measurements of passive cavities fabricated in silicon. For microcavities operating in the lambda = 1500 nm wavelength band, quality factors between 1.3-4.0x10(4) are measured for significant variations in cavity geometry and for resonant mode normalized frequencies shifted by as much as 10% of the nominal value. PMID- 19474970 TI - Electronic color charts for dielectric films on silicon. AB - This paper presents the calculation of the perceived color of dielectric films on silicon. A procedure is shown for computing the perceived color for an arbitrary light source, light incident angle, and film thickness. The calculated color is converted into RGB parameters that can be displayed on a color monitor, resulting in the generation of electronic color charts for dielectric films. This paper shows generated electronic color charts for both silicon dioxide and silicon nitride films on silicon. PMID- 19474971 TI - Fast, large and controllable phase modulation using dual frequency liquid crystals. AB - We report on a method for high speed, large stroke phase modulation using dual frequency control of liquid crystals. Our system uses an all-electronic feedback system in order to simplify the control. We show half wave phase modulations of ~120Hz with the operating point varying over nearly the full dynamic range of the device, and demonstrate larger phase shifts (2.5 waves) at a frequency of 37Hz. For large phase shifts, the speeds are an order of magnitude faster than existing techniques. PMID- 19474972 TI - Introduction. AB - Photonic crystal materials attracted much attention during last years with the number of publications and patents increasing exponentially. Two-dimensional (2D) photonic crystal structures, like holey fibers and 2D slab-type photonic crystals, are probably the most advanced and fast developing areas owing to mature fabrication methods and envisioned broad applications. They are now at a critical phase of their development as they move fast from the realm of fundamental studies to photonic devices and commercialization. The idea behind this issue is to look at both fiber and 2D waveguide geometries and explore some of the most important and interesting issues related to implementation of these optical structures as photonic devices. This special issue is inspired by a recent LEOS Topical Meeting on this topic held in Vancouver in July 2003. The meeting was very stimulating and challenged many perceptions of the role of photonic crystal technologies in next generation photonic devices. We have invited a good mix of theoretical, experimental and optical device contributions, both from the photonic crystal community as well as the holey fiber community with the intention that this special issue will catalyze the rapid advance of our subject and bring together these different fields to foster research strength. PMID- 19474973 TI - Hollow core photonic crystal fibers for beam delivery. AB - Hollow-core photonic crystal fibers have unusual properties which make them ideally suited to delivery of laser beams. We describe the properties of fibers with different core designs, and the observed effects of anti-crossings with interface modes. We conclude that 7-unit-cell cores are currently most suitable for transmission of femtosecond and sub-picosecond pulses, whereas larger cores (e.g. 19-cell cores) are better for delivering nanosecond pulsed and continuous wave beams. PMID- 19474974 TI - Surface modes in air-core photonic band-gap fibers. AB - We present a detailed description of the role of surface modes in photonic band gap fibers (PBGFs). A model is developed that connects the experimental observations of high losses in the middle of the transmission spectrum to the presence of surface modes supported at the core-cladding interface. Furthermore, a new PBGF design is proposed that avoids these surface modes and produces single mode operation. PMID- 19474975 TI - Reflection symmetry and mode transversality in microstructured fibers. AB - We investigate the influence of reflection symmetry on the properties of the modes of microstructured optical fibers. It is found that structures with reflection symmetry tend to support non-degenerate modes which are closer in nature to the analogous TE and TM modes of circular step-index fibers, as compared with fibers with only rotational symmetry. Reflection symmetry induces modes to exhibit smaller longitudinal components and transverse fields which are more strongly reminiscent of the radial and azimuthal modes of circular fibers. The tendency towards "transversality" can be viewed as a result of the interaction of group theoretical restrictions on the mode profiles and minimization of the Maxwell Hamiltonian. PMID- 19474976 TI - Hollow multilayer photonic bandgap fibers for NIR applications. AB - Here we report the fabrication of hollow-core cylindrical photonic bandgap fibers with fundamental photonic bandgaps at near-infrared wavelengths, from 0.85 to 2.28 microm. In these fibers the photonic bandgaps are created by an all-solid multilayer composite meso-structure having a photonic crystal lattice period as small as 260 nm, individual layers below 75 nm and as many as 35 periods. These represent, to the best of our knowledge, the smallest period lengths and highest period counts reported to date for hollow PBG fibers. The fibers are drawn from a multilayer preform into extended lengths of fiber. Light is guided in the fibers through a large hollow core that is lined with an interior omnidirectional dielectric mirror. We extend the range of materials that can be used in these fibers to include poly(ether imide) (PEI) in addition to the arsenic triselenide (As(2)Se(3)) glass and poly(ether sulfone) (PES) that have been used previously. Further, we characterize the refractive indices of these materials over a broad wavelength range (0.25 - 15 microm) and incorporated the measured optical properties into calculations of the fiber photonic band structure and a preliminary loss analysis. PMID- 19474977 TI - Optical bistability and cutoff solitons in photonic bandgap fibers. AB - We present detailed theoretical and numerical analysis of certain novel non linear optical phenomena enabled by photonic bandgap fibers. In particular, we demonstrate the feasibility of optical bistability in an axially modulated nonlinear photonic bandgap fiber through analytical theory and detailed numerical experiments. At 1.55microm carrier wavelength, the in-fiber devices we propose can operate with only a few tens of mW of power, have a nearly instantaneous response and recovery time, and be shorter than 100microm. Furthermore, we predict existence of gap-like solitons (which have thus-far been described only in axially periodic systems) in axially uniform photonic bandgap fibers. PMID- 19474978 TI - A new slant on photonic crystal fibers. AB - We present the novel use of microstructured optical fibers not as "light-pipes", but in a transverse geometry to manipulate the light propagating across the fiber. Fundamental and higher-order bandgaps were observed experimentally in this geometry using a number of techniques. The comparison of the measured spectra with photonic band structure and Finite-Difference Time-Domain simulations provide strong evidence that the spectral features are a result of the periodic nature of the fiber microstructure in the transverse direction. PMID- 19474979 TI - Application of an ARROW model for designing tunable photonic devices. AB - Microstructured optical fibers with the low refractive index core surrounded by high refractive index cylindrical inclusions reveal several intriguing properties. Firstly, there is a guiding regime in which the fibers' confinement loss is strongly dependent of wavelength. In this regime, the positions of loss maxima are largely determined by the individual properties of high index inclusions rather than their position and number. Secondly, the spectra of these fibers can be tuned by changing the refractive index of the inclusions. In this paper we review transmission properties of these fibers and discuss their potential applications for designing tunable photonic devices. PMID- 19474980 TI - Waveguides, resonators and their coupled elements in photonic crystal slabs. AB - The design, fabrication, and measurement of photonic-band-gap (PBG) waveguides, resonators and their coupled elements in two-dimensional photonic crystal (PhC) slabs have been investigated. We have studied various loss mechanisms in PBG waveguides and have achieved a very low propagation loss (~1 dB/mm). For these waveguides, we have observed a large group delay (>100 ps) by time-domain measurement. As regards PBG resonators, we realize very high-Q and small volume resonators in PhC slabs by appropriate design. Finally, we demonstrate various forms of coupled elements of waveguides and resonators: 2-port resonant-tunneling transmission devices, 4-port channel-drop devices using the slow light mode, and 3-port channel-drop devices using the resonant-tunneling process. PMID- 19474981 TI - Room temperature continuous wave operation of a surface-emitting two-dimensional photonic crystal diode laser. AB - We achieved room temperature continuous wave operation of a surface-emitting two dimensional photonic crystal diode laser by current injection. This is the first time ever that room temperature continuous wave operation of a photonic crystal diode laser has been realized. This laser features single mode oscillation over a large area, which is impossible for conventional lasers. In this work, we optimized the epitaxial layer composition for better carrier confinement and clarified the relationship between the diameter of the air holes in the photonic crystal and the threshold current of the laser in order to estimate the optimized threshold current. PMID- 19474982 TI - Enhanced gain measurement at mode singularities in InP-based photonic crystal waveguides. AB - We present a method of direct measurement of spectral gain and corresponding data in photonic crystal waveguides defined in heterostructures on InP substrates. The method makes use of two photopumping beams, one for gain generation, the other for amplification probing. The results show a clear enhancement of gain at spectral regions of low-group velocity, namely at the edges of the so-called mini stopband of a three-missing rows wide photonic crystal waveguide. PMID- 19474983 TI - Angular and polarization properties of a photonic crystal slab mirror. AB - It was recently demonstrated that a photonic crystal slab can function as a mirror for externally incident light along a normal direction with near-complete reflectivity over a broad wavelength range. We analyze the angular and polarization properties of such photonic crystal slab mirror, and show such reflectivity occurs over a sizable angular range for both polarizations. We also show that such mirror can be designed to reflect one polarization completely, while allowing 100% transmission for the other polarization, thus behaving as a polarization splitter with a complete contrast. The theoretical analysis is validated by comparing with experimental measurements. PMID- 19474984 TI - Basic structures for photonic integrated circuits in Silicon-on-insulator. AB - For the compact integration of photonic circuits, wavelength-scale structures with a high index contrast are a key requirement. We developed a fabrication process for these nanophotonic structures in Silicon-on-insulator using CMOS processing techniques based on deep UV lithography. We have fabricated both photonic wires and photonic crystal waveguides and show that, with the same fabrication technique, photonic wires have much less propagation loss than photonic crystal waveguides. Measurements show losses of 0.24dB/mm for photonic wires, and 7.5dB/mm for photonic crystal waveguides. To tackle the coupling to fiber, we studied and fabricated vertical fiber couplers with coupling efficiencies of over 21%. In addition, we demonstrate integrated compact spot size converters with a mode-to-mode coupling efficiency of over 70%. PMID- 19474985 TI - Photonic crystal devices modelled as grating stacks: matrix generalizations of thin film optics. AB - A rigorous semi-analytic approach to the modelling of coupling, guiding and propagation in complex microstructures embedded in two-dimensional photonic crystals is presented. The method, which is based on Bloch mode expansions and generalized Fresnel coefficients, is shown to be able to treat photonic crystal devices in ways which are analogous to those used in thin film optics with uniform media. Asymptotic methods are developed and exemplified through the study of a serpentine waveguide, a potential slow wave device. PMID- 19474986 TI - All-optical tunability of a nonlinear photonic crystal channel drop filter. AB - We report a numerical analysis of an optically tunable channel drop filter that consists of a resonant cavity side-coupled to a waveguide embedded in a two dimensional nonlinear photonic crystal. We first introduce a numerical method that allows us to calculate the photonic band structure of a nonlinear photonic crystal, as well as the frequency and field profile of cavity and waveguide modes. Then, we use this numerical method to study the dependence of the resonant frequency of a cavity side-coupled to a waveguide, on the optical power in the waveguide. PMID- 19474987 TI - Nonlinear transmission of 1.5 microm pulses through single-mode silicon-on insulator waveguide structures. AB - An 80 MHz pulse train of ~ 100 fs optical pulses centred at ~ 1.5 microm is propagated through a variety of high-index-contrast silicon-on-insulator waveguide structures less than 1 mm long. All-optical power limiting and negative differential transmission, based only on the intrinsic nonlinear response of the untextured waveguides near 1.5 microm, are demonstrated for average in-guide power levels of ~ 1 mW. Superlinear transmission is observed in a textured silicon waveguide for power levels less than 20 microW. PMID- 19474988 TI - Losses in single-mode silicon-on-insulator strip waveguides and bends. AB - We report the fabrication and accurate measurement of propagation and bending losses in single-mode silicon waveguides with submicron dimensions fabricated on silicon-on-insulator wafers. Owing to the small sidewall surface roughness achieved by processing on a standard 200mm CMOS fabrication line, minimal propagation losses of 3.6+/-0.1dB/cm for the TE polarization were measured at the telecommunications wavelength of 1.5microm. Losses per 90 masculine bend are measured to be 0.086+/-0.005dB for a bending radius of 1microm and as low as 0.013+/-0.005dB for a bend radius of 2microm. These record low numbers can be used as a benchmark for further development of silicon microphotonic components and circuits. PMID- 19474989 TI - Compression of 3D color integral images. AB - In this paper, we discuss the compression results of full color 3D Integral Images (II) by MPEG-2 (Motion Picture Experts Group). II is a popular three dimensional image video recording and display technique. The huge size of II data has become a practical issue for storing and transmitting of 3D scenes. The MPEG is a standard coded representation of moving pictures. We model the elemental images in II as consecutive frames in a moving picture. Therefore, MPEG scheme can be applied to take advantage of the high cross-correlations between elemental images. We also introduce several scanning topologies along the elemental image sequences and investigate their performance with different number of pictures in GOP (Group of Picture). Experimental results are presented to illustrate the image quality of the MPEG-2 and the baseline JPEG with the same compression rate. We show that a well-known and widely-available MPEG-2 scheme can be a good alternative for II compression. PMID- 19474990 TI - Multispectral imaging using compact compound optics. AB - A very thin image capturing system called TOMBO (thin observation module by bound optics) is developed with compound-eye imaging and digital post-processing. As an application of TOMBO, a multispectral imaging system is proposed. With a specific arrangement of the optical system, spatial points can be observed by multiple photodetectors simultaneously. A filter array inserted in front of the image sensor enables observation of the spectrum of the target. The captured image is reconstructed by a modified pixel rearranging method extended to treat multi channel spectral data, in which pixels in the captured image are geometrically rearranged onto a multi-channel virtual image plane. Experimental results of the image reconstruction show the effectiveness of the proposed system. PMID- 19474991 TI - Stiffness analysis in the numerical solution of Raman amplifier propagation equations. AB - For the first time, the stiffness of Raman amplifier propagation equations is analyzed. And based on this analysis, a novel method for propagation equations is proposed to enhance the stability of numerical simulation. To verify the reliability of this method, simulation experiments are employed by using our method and the existent predictor-corrector method with comparison. The results show that our backward differentiation formulae method behaves much better in stability with a comparative accuracy. PMID- 19474992 TI - Interactive application in holographic optical tweezers of a multi-plane Gerchberg-Saxton algorithm for three-dimensional light shaping. AB - Phase-hologram patterns that can shape the intensity distribution of a light beam in several planes simultaneously can be calculated with an iterative Gerchberg Saxton algorithm [T. Haist et al., Opt. Commun. 140, 299 (1997)]. We apply this algorithm in holographic optical tweezers. This allows us to simultaneously trap several objects in individually controllable arbitrary 3-dimensional positions. We demonstrate the interactive use of our approach by trapping microscopic spheres and moving them into an arbitrary 3-dimensional configuration. PMID- 19474993 TI - Modelling the bidirectional reflectance distribution function (BRDF) of seawater polluted by an oil film. AB - The Bi-directional Reflectance Distribution Function (BRDF) of both clean seawaters and those polluted with oil film was determined using the Monte Carlo radiative transfer technique in which the spectrum of complex refractive index of Romashkino crude oil and the optical properties of case II water for chosen wavelengths was considered. The BRDF values were recorded for 1836 solid angular sectors of throughout the upper hemisphere. The visibility of areas polluted with oil observed from various directions and for various wavelengths is discussed. PMID- 19474994 TI - Precision of extracting absorption profiles from weakly scattering media with spectroscopic time-domain optical coherence tomography. AB - The feasibility of spectroscopic optical coherence tomography (SOCT) to quantify spatially localized absorption profiles of chromophores embedded in weakly scattering media with a single measurement over the full spectral bandwidth of the light source was investigated by using a state-of-the-art ultra-broad bandwidth Ti:Al(2)O(3) laser (lambdac = 800 nm, Deltalambda = 260 nm, P(out) = 120 mW ex-fiber). The precision of the method as a function of the chromophore absorption, the sample thickness, and different parameters related to the measurement procedure was evaluated both theoretically and experimentally in single and multilayered phantoms. It is demonstrated that in weakly scattering media SOCT is able to extract mua(lambda) as small as 0.5 mm-1 from 450 mum thick phantoms with a precision of ~2% in the central and ~8% at the edges of the used wavelength region. As expected, in phantoms with the same absorption properties and thickness ~180 mum the precision of SOCT decreases to >10% in the central wavelength region. PMID- 19474995 TI - Multiconjugate adaptive optics: laboratory experience. AB - We present the results from a laboratory multiconjugate adaptive optics experiment. The experiment is differentiated from other published work in that it has a programmable deterministic turbulence generator and an output science camera. The turbulence was generated using a dual layer turbulence emulator, and then corrected using an AO system with 2 wavefront correctors and a Shack-Hartman wavefront sensor, which processed information from five artificial guide stars. We report our results and also describe some of the problems. PMID- 19474996 TI - Group velocity dispersion of tapered fibers immersed in different liquids. AB - We investigate the group velocity dispersion of tapered fibers that are immersed in different liquids. Using the Sellmeier equations fitted from measured refractive indices of these liquids, we are able to analyze the dispersion characteristics of the tapered fibers in a tailored liquid environment. Theoretical results show a large span of slowly varying anomalous group velocity dispersion characteristics. This leads to potentially significant improvements and a large bandwidth in supercontinuum generation in a tapered fiber. This holds true as well for a range of new fiber materials. PMID- 19474997 TI - High quality-factor whispering-gallery mode in the photonic crystal hexagonal disk cavity. AB - We study whispering-gallery-like modes in photonic crystal air-bridge slab micro cavities having H2 defects using finite-difference time-domain calculations. The defect geometry is optimized to increase the quality factor (Q) of the H2-cavity whispering-gallery mode (WGM). By symmetrically distributing 12 nearest neighbor holes around the defect and controlling size of holes, it is possible to drastically increase the Q of >10(5) while preserving effective mode volume of the order of the cubic wavelength in material. In addition, we investigate the effect of a dielectric circular post located around the center of the H2 cavity. This post can act as current and heat flow paths that promise electrically-pumped thermally-stable lasing operation. It is interesting to observe that the introduction of the post structure increases the Q of the WGM up to 4x10(5) and the high Q >10(5) is still maintained even with large post size. Although diffractive out-coupling through the post is increased, radiated power outside the post is suppressed, which leads to large enhancement of the Q of the H2 cavity WGM. PMID- 19474998 TI - Form birefringence in UV-exposed photosensitive fibers computed using a higher order finite element method. AB - The effective index change and form birefringence are calculated in UV-exposed fibers using a high-order vectorial finite element method. The birefringence is compared in optical fibers with and without photosensitive inner cladding. PMID- 19474999 TI - Finite element method for diffusive light propagations in index-mismatched media. AB - Near-infrared (NIR) light propagations in strongly scattering tissue have been studied in the past few decades and diffusion approximations (DA) have been extensively used under the assumption that the refractive index is constant throughout the medium. When the index is varying, the discontinuity of the fluence rate arises at the index-mismatched interface. We introduce the finite element method (FEM) incorporating the refractive index mismatch at the interface between the diffusive media without any approximations. Intensity, mean time, and mean optical path length were computed by FEM and by Monte Carlo (MC) simulations for a two-layer slab model and a good agreement between the data from FEM and from MC was found. The absorption sensitivity of intensity and mean time measurements was also analyzed by FEM. We have shown that mean time and absorption sensitivity functions vary significantly as the refractive index mismatch develops at the interface between the two layers. PMID- 19475000 TI - Photonic band gap analysis using finite-difference frequency-domain method. AB - A finite-difference frequency-domain (FDFD) method is applied for photonic band gap calculations. The Maxwell's equations under generalized coordinates are solved for both orthogonal and non-orthogonal lattice geometries. Complete and accurate band gap information is obtained by using this FDFD approach. Numerical results for 2D TE/TM modes in square and triangular lattices are in excellent agreements with results from plane wave method (PWM). The accuracy, convergence and computation time of this method are also discussed. PMID- 19475001 TI - Investigation of Raman fiber laser temperature probe based on fiber Bragg gratings for long-distance remote sensing applications. AB - We demonstrate a practical and simple, all fiber Bragg grating (FBG) based Raman laser sensing probe for long-distance, remote temperature sensing application. Using multiple laser cavities based on FBG's and a tunable chirped FBG, we obtain the simultaneous multi-channel remote temperature sensing operation at a 50 km distance. The temperature sensitivity is measured to be 7.15 pm/ degrees C. PMID- 19475002 TI - Thermal oxide based silica ridge waveguide. AB - A silica planar waveguide structure, where a ridge waveguide resides on a vacuum gap, was invented. The silica layer, which was fabricated through thermal oxidation at 1150 masculineC, had an excellent optical index uniformity on the order of 3x10(-5) @1550 nm, and a thickness uniformity of 10 nm at a thickness of 10 microm. Straight waveguide with low insertion loss was demonstrated. Improved thermal efficiency of this structure to cause phase change was discussed in comparison to the conventional channel waveguide structure. Finally, the limitation of this technology to make complex device structures was also explored. PMID- 19475003 TI - Period doubling and deterministic chaos in continuously pumped regenerative amplifiers. AB - Multi-energy and chaotic pulse energy output from a continuously pumped regenerative amplifier is observed for dumping rates around the inverse upper state lifetime of the gain medium. The relevant regimes of operation are analyzed numerically and experimentally in a diode-pumped Yb:glass regenerative amplifier. The boundaries between stable and unstable pulsing are identified and stability criteria in dependence on the amplifier gate length and pump power are discussed. PMID- 19475004 TI - Bloch method for the analysis of modes in microstructured optical fibers. AB - We discuss a transform technique for analyzing the wave vector content of microstructured optical fiber (MOF) modes, which is computationally efficient and gives good physical insight into the nature of the mode. In particular, if the mode undergoes a transition from a bound state to an extended state, this is evident in the spreading-out of its transform. The method has been implemented in the multipole formulation for finding MOF modes, but are capable of adaptation to other formulations. PMID- 19475005 TI - Predicting macrobending loss for large-mode area photonic crystal fibers. AB - We report on an easy-to-evaluate expression for the prediction of the bend-loss for a large mode area photonic crystal fiber (PCF) with a triangular air-hole lattice. The expression is based on a recently proposed formulation of the V parameter for a PCF and contains no free parameters. The validity of the expression is verified experimentally for varying fiber parameters as well as bend radius. The typical deviation between the position of the measured and the predicted bend loss edge is within measurement uncertainty. PMID- 19475006 TI - Acrylamide-N,N'-methylenebisacrylamide silica glass holographic recording material. AB - In this paper, we describe a photopolymerizable silica glass based on acrylamide (AA) and N,N'-methylenebisacrylamide (BMA) as monomers, triethanolamine (TEA) as coinitiator and yellowish eosin (YE) as photoinitiator. We studied different compositions, analyzing the diffraction efficiency, energetic exposure and effective thickness obtained in the holographic gratings. A diffraction efficiency of 60 % with an energetic exposure of 139 mJ/cm(2) and an effective thickness of 1.1 mm were obtained. Also, by varying the photopolymerizable composition of the material diffraction efficiencies higher than 80 % can be reached with an energetic exposure of 10 mJ/cm(2) and an effective thickness of 113 microm. These values are similar to those obtained in conventional photopolymer systems in polyvinylalcohol and better than the values reached in other sol-gel compositions. Also, 9 holograms were angular multiplexed with diffraction efficiencies between 6 and 12 % and total exposure time shorter than 150 ms, with a dynamic range M/#= 2.4. PMID- 19475007 TI - One-unit system for electroholography by use of a special-purpose computational chip with a high-resolution liquid-crystal display toward a three-dimensional television. AB - We developed a one-unit system for electroholography, which consists of a special purpose computational chip and a high-resolution, reflective mode, liquid-crystal display panel as a spatial light modulator. We implemented them on one board whose size is approximately 20 cm x 20 cm. The chip makes a computer-generated hologram whose size is 800 x600 at nearly real time (~0.5 s) for an object consisting of 1000 points. The pixel pitch of the display panel is 12 microm, and the resolution is 800 x 600. It reconstructs a three-dimensional motion image whose size is approximately 3 cm x 3 cm x 3 cm. The system can be readily scaled up, since the units consisting of the chip and the display are easily set in parallel. PMID- 19475008 TI - Investigation and optimization of bidirectionally dual-order pumped distributed Raman amplifiers. AB - A theoretical investigation of bidirectionally dual-order pumped distributed Raman amplifiers is presented in detail, and comparisons with other Raman amplification schemes, i.e., bidirectional first-order pumping and Raman-plus erbium-doped fiber hybrid amplification, are carried out, for the first time to the authors' knowledge, at identical nonlinear phase shifts. The results show that symmetric bidirectional dual-order pumping can achieve the best optical signal-to-noise ratio performance by appropriate choice of the second-order pump wavelength and second-to-first-order pump power ratio for both short- and long span conditions, which will be helpful for designing long-haul transmission systems. PMID- 19475009 TI - Quasi-direct writing of diffractive structures with a focused ion beam. AB - A new method for fabrication of diffractive structures, which we call quasi direct writing, is illustrated. The diffractive structures can be generated by changing the pixel spacing along the direction of the cross scan (with zero overlap) and keeping the pixel spacing constant along the other scan direction, with a normal overlap of 50%-60%, while the substrate surface is scanned with a focused ion beam (FIB). Quasi-direct writing is a method for achieving special customer designs when the milling machine has no computer programming function. Diffractive structures with various periods and depths can be derived by controlling the parameters of pixel spacing, beam current, ion incidence angle, and the scan time or ion dose. The method is not restricted to any one material and can be used for metals, insulators, and semiconductors. PMID- 19475010 TI - Lithographic fabrication of large curved hologram by laser writer. AB - We fabricated a large curved computer-generated hologram pattern on the concave substrate with diameter of 110mm and radius of curvature of 504mm. The line width of the hologram varied form 39um to 810um. We adopt the single pass and the screw lines to fabricate this curved hologram precisely and efficiently. 80% of the fabrication time is saved by this method. This work will be useful to the measurement of large convex secondary mirrors that is also hardness at present. PMID- 19475011 TI - All fiber optical inter-band router for broadband wavelength division multiplexing. AB - We propose a new type of all-fiber device for inter-band router using a novel hybrid waveguide-MEMS technology. Both continuous and discrete band-routing functions are realized by precise twist control over the fused coupling region, which results in pi phase shift between the output ports. Experimentally we demonstrate inter-band routing functions between O and C-band as well as between E and L-band with a low insertion loss, wide bandwidth of operation, high channel isolation and fast response. PMID- 19475012 TI - Analysis of splitters for self-collimated beams in planar photonic crystals. AB - In this paper, we present methods for beam splitting in a planar photonic crystal, where the light is self-guided as dictated by the selfcollimation phenomenon. We present an analysis of a one-to-two and one-to-three beam splitter in a self-guiding photonic crystal lattice and validate our design and simulations with experimental results. Moreover, we present the first one-to three splitter in a self-guiding planar photonic crystal. Additionally, we discuss the ability to tune the properties of these devices and present initial experimental results. PMID- 19475013 TI - In-situ visualization, monitoring and analysis of electric field domain reversal process in ferroelectric crystals by digital holography. AB - In-situ monitoring of domain reversal in congruent lithium niobate by a digital holographic technique is described. While the ferroelectric polarization is reversed by electric field poling, the two-dimensional distribution of the phase shift, due mainly to the linear electro-optic and piezoelectric effects, is measured and visualized. Digital holography is used to reconstruct both amplitude and phase of the wavefield transmitted by the sample to reveal the phase shift induced by adjacent reversed domains during the poling. The resulting movies of both amplitude and phase maps, for in-situ visualization of domain pattern formation, are shown. The possibility of using the technique as tool for monitoring in real-time the periodic poling of patterned samples is discussed. PMID- 19475014 TI - Multiple-color cw visible lasers by frequency sum-mixing in a cascading Raman fiber laser. AB - Multiple cw visible lasers at wavelengths ranging from 550nm to 625nm were generated by intracavity frequency sum-mixing of a cascading Raman fiber laser in a type-I noncritically phase-matched lithium triborate crystal. The phase matching conditions for individual wavelengths were realized by tuning the temperature of the lithium triborate crystal. PMID- 19475015 TI - All-optical differential detection for suppressing multiple-access interference in coherent time-addressed optical CDMA systems. AB - A novel scheme for suppressing the multiple-access interference (MAI) in coherent time-addressed optical CDMA systems is proposed. This is based on a differential detection using the dual-control NOLM. The basic principle for MAI suppression is described. For experimental demonstration, two encoded channels are constructed and decoded. These decoded signals are sent to the dual-control NOLM and a high autocorrelation peak with suppressed MAI at the output of NOLM is observed. Signal-to-interference ratio is improved by 7 dB. PMID- 19475016 TI - Lasing in chiral photonic liquid crystals and associated frequency tuning. AB - This letter addresses a dye-doped planar cholesteric cell as a one-dimensional photonic crystal, which can be lased at the band edges of the photonic band gap. The effect of the composition of the material and the thickness of a cholesteric cell (CLC) on the lasing action, and the photo-control of the lasing frequency, are experimentally investigated. Adding a tunable chiral monomer (TCM) allows the CLC's reflection band to be tuned by varying the intensity and/or exposure time of the UV curing light, enabling the lasing frequency of the CLC sample to be tuned. PMID- 19475017 TI - Simple geometric criterion to predict the existence of surface modes in air-core photonic-bandgap fibers. AB - We propose a simple geometric criterion based on the size of the core relative to the photonic crystal to quickly determine whether an air-core photonic-bandgap fiber with a given geometry supports surface modes. Comparison to computer simulations show that when applied to fibers with a triangular-pattern cladding and a circular air core, this criterion accurately predicts the existence of a finite number of discrete ranges of core radii that support no surface modes. This valuable tool obviates the need for time-consuming and costly simulations, and it can be easily applied to fibers with an arbitrary photonic-crystal structure and core profile. PMID- 19475018 TI - Phosphorescence-Fluorescence ratio imaging for monitoring the oxygen status during photodynamic therapy. AB - The effectiveness of photodynamic therapy is strongly dependent on the availabilty of oxygen. In the present paper we show that the ratio between photosensitiser phosphorescence and fluorescence is a parameter that can be used to monitor the competition between singlet oxygen production and other processes quenching the photosensitiser triplet state. We present a theoretical basis for the validity of this approach and a series of in vitro imaging experiments. PMID- 19475019 TI - Imaging with a Terahertz quantum cascade laser. AB - We demonstrate bio-medical imaging using a Terahertz quantum cascade laser. This new optoelectronic source of coherent Terahertz radiation allows building a compact imaging system with a large dynamic range and high spatial resolution. We obtain images of a rat brain section at 3.4 THz. Distinct regions of brain tissue rich in fat, proteins, and fluid-filled cavities are resolved showing the high contrast of Terahertz radiation for biological tissue. These results suggest that continuous-wave Terahertz imaging with a carefully chosen wavelength can provide valuable data on samples of biological origin; these data appear complementary to those obtained from white-light images. PMID- 19475020 TI - Use of nondegenerate resonant leaky modes to fashion diverse optical spectra. AB - In this paper, we show that bandstop and bandpass filters with versatile spectral attributes can be implemented with modulated films possessing asymmetric grating profiles. The profile asymmetry breaks the resonant leaky mode degeneracy at normal incidence thereby permitting precise spectral spacing of interacting leaky modes with interesting implications in optical filter design. Several example filters, containing only a single grating layer, are designed with this methodology to demonstrate the concept. PMID- 19475021 TI - Minimally invasive optical beam profiler. AB - Proposed and demonstrated is a minimally invasive optical beam profiler using a non-pixelated liquid crystal spatial light modulator. The profiler features high detection sensitivity in the visible band, high 50 lines/mm spatial resolution, beam observation zone 100 % fill factor and magnification flexibility, and video rate operations. Applications for this beam profiler includes plug and test beam measurements with minimal interruptions and feedback effects introduced into the optical beam system under test. PMID- 19475022 TI - Flexibly tunable multichannel filter and bandpass filter based on long-period fiber gratings. AB - The voltage-controllable multichannel filter based on multiply cascaded long period fiber gratings with a divided coil heater will be proposed and experimentally demonstrated. It has several advantages of the large tuning range in both C- and L-band, multichannel operation, multiwavelength electivity, and bandwidth controllability. The tunable bandpass filter based on long-period fiber gratings ith the broad bandwidth over 6.5 nm, large tuning range over 30 nm, and excellent side mode suppression more than 40 dB will be also discussed. PMID- 19475023 TI - Arbitrary micropatterning method in femtosecond laser microprocessing using diffractive optical elements. AB - We successfully developed an arbitrary micro-patterning method with femtosecond pulses using a multi-level phase type diffractive optical element (DOE) and a focusing objective lens. The large chromatic dispersion effects of DOE resulting from the spectral bandwidth of femtosecond pulses can be reduced with the appropriate DOE focal length and the proper distance between the DOE and the focusing lens. The method was verified through optical and processing experiments. A partial periodic structure was formed at the designated position. Microstructures were precisely formed on the SiO2 glass surface and inside the glass by irradiating the constructed beam. The points were evenly dispersed with a separation of 5 mum. PMID- 19475024 TI - High birefringence in elliptical hollow optical fiber. AB - We propose a novel design of highly birefringent optical fiber composed of a central elliptical air hole, a circumferential elliptical ring core, and a circular cladding. The proposed waveguide structure is predicted to produce a linear birefringence higher by an order of magnitude than the solid elliptical core fiber. The large index contrast between the central air and germanosilica elliptical ring core is mainly attributed to the high birefringence and its characteristics are theoretically analyzed in terms of its waveguide parameters. PMID- 19475025 TI - Optical properties of injection molded subwavelength gratings. AB - We have fabricated injection molded subwavelength gratings for anti-reflection purposes superimposed upon a blazed grating structure in polycarbonate. The gratings are initially formed by electron-beam lithography and subsequently replicated using injection molding. There are several problems when trying to optically characterize a component such as a blazed transmittance grating. Standard spectrophotometers are not well suited for measuring transmittance in the different diffraction orders individually. Our sample size of 0.8x0.8 mm(2) is also a problem for standard instruments. First order transmittance has been measured for blazed gratings with single and double-sided AR-treatment and is transmittance is compared with with higher diffraction orders. Double-sided AR treatment not only increase the total transmittance but also widens the wavelength range with high effectiveness of the first order diffraction. PMID- 19475026 TI - Frequency-tunable anti-Stokes line emission by eigenmodes of a birefringent microstructure fiber. AB - Birefringent microstructure fibers are shown to allow efficient generation of frequency-tunable anti-Stokes line emission as a result of nonlinear-optical spectral transformation of unamplified femtosecond Ti: sapphire laser pulses. Femtosecond pulses of 820-nm pump radiation polarized along the fast and slow axes of the elliptical core of the microstructure fiber generate intense blue shifted lines centered at 490 and 510 nm, respectively, observed as bright blue and green emission at the output of a 10-cm microstructure fiber. PMID- 19475027 TI - Simultaneous nonlinearity suppression and wide-band dispersion compensation using optical phase conjugation. AB - Optical phase conjugation is demonstrated to enable simultaneous wide-band compensation of the residual dispersion and the fiber nonlinearities in dispersion-managed fiber transmission lines employing slope-compensating fibers. When the dispersion slope of transmission fibers is equalized by slope compensating fibers, the residual dispersion and the slope of dispersion slope are compensated by middle-span optical phase conjugation. More importantly, fiber nonlinearity may be largely suppressed by arranging the fibers into conjugate pairs about the phase conjugator, where the two fibers of each pair are in scaled translational symmetry. The translational symmetry is responsible for cancelling optical nonlinearities of the two fibers up to the first-order perturbation, then a mirror-symmetric ordering of the fiber pairs about the conjugator linearizes a long transmission line effectively. PMID- 19475028 TI - Numerical simulation of an optical resonator for generation of a doughnut-like laser beam. AB - A design of an optical resonator for generation of a doughnutlike laser beam in the far field is proposed. The resonator consists of a toric mirror, a flat output coupler, and a w-axicon with a movable center axicon. Two-dimensional vector electric field simulation has shown that any one of the Laguerre-Gaussian modes can be selected by sliding the center axicon. Therefore this resonator is capable of generating doughnut-like laser beams, whose dark spot size can be controlled in real time. This feature of the proposed resonator is advantageous for atom trapping and optical tweezers. PMID- 19475029 TI - Solution doping of microstructured polymer optical fibres. AB - Solution doping of microstructured polymer optical fibres [mPOF] is demonstrated, a technique which allows dopants to be introduced after polymerisation through the microstructure. Controlled diffusion is used to disperse the dopant uniformly across the fibre core, and the final concentration can be systematically varied by appropriate choice of conditions. We use this technique to produce a fibre doped with Rhodamine 6G and characterize its loss and fluorescence behavior. PMID- 19475030 TI - Polarization mode dispersion reduction in spun large mode area silica holey fibres. AB - We report the fabrication of the first spun holey optical fibre. Our experiments show that the complex air/glass transverse structure can be retained when the preform is spun during the fibre drawing process. Measurements of differential group delay (DGD) confirm that significant reductions in polarization mode dispersion (PMD) can be readily achieved using this approach. PMID- 19475031 TI - Processing carbon nanotubes with holographic optical tweezers. AB - We report the first demonstration that carbon nanotubes can be trapped and manipulated by optical tweezers. This observation is surprising because individual nanotubes are substantially smaller than the wavelength of light, and thus should not be amenable to optical trapping. Even so, nanotube bundles, and perhaps even individual nanotubes, can be transported at high speeds, deposited onto substrates, untangled, and selectively ablated, all with visible light. The use of holographic optical tweezers, capable of creating hundreds of independent traps simultaneously, suggests opportunities for highly parallel nanotube processing with light. PMID- 19475032 TI - Efficient, diode-pumped Tm(3)+:BaY(2)F(8) vibronic laser. AB - In this work we report the spectroscopy and laser results of several Thulium doped BaY(2)F(8) single crystals grown using the Czochralski technique. The doping concentration is between 2at.% and 18at.%. We performed room temperature laser experiments pumping the samples with a laser diode at 789 nm obtaining 61% as maximum optical-to-optical efficiency with a maximum output power of 290 mW and a minimum lasing threshold of 26 mW. The lasing wavelength changed with the dopant concentration from 1927 nm up to 2030 nm and the nature of the transition changed from purely electronic to vibronic, accordingly. PMID- 19475033 TI - Photonic crystal fiber design by means of a genetic algorithm. AB - A Genetic Algorithm (GA) is used to design photonic crystal fiber structures with user-defined chromatic dispersion properties. This GA is combined with a full vectorial finite element method in order to determine the effective index of propagation of the modes and then, the chromatic dispersion of structures generated by GA. This method proves to be a powerful tool for solving this inverse problem. PMID- 19475034 TI - Topology optimization and fabrication of photonic crystal structures. AB - Topology optimization is used to design a planar photonic crystal waveguide component resulting in significantly enhanced functionality. Exceptional transmission through a photonic crystal waveguide Z-bend is obtained using this inverse design strategy. The design has been realized in a silicon-on-insulator based photonic crystal waveguide. A large low loss bandwidth of more than 200 nm for the bandgap polarization is experimentally confirmed. PMID- 19475035 TI - High temperature-gradient refractive index liquid crystals. AB - We have analyzed the physical origins of the temperature gradient of the ordinary refractive index ( dn(o) /dT) of liquid crystals. To achieve a large dn(o) /dT , high birefringence and low clearing temperature play crucial roles. Based on these simple guidelines, we formulated two exemplary liquid crystal mixtures, designated as UCF-1 and UCF-2, and compared their physical properties with a commonly used commercial liquid crystal compound 5CB. The dn(o) /dT of UCF-1 is ~4X higher than that of 5CB at room temperature. PMID- 19475036 TI - Quantum key distribution with 1.25 Gbps clock synchronization. AB - We have demonstrated the exchange of sifted quantum cryptographic key over a 730 meter free-space link at rates of up to 1.0 Mbps, two orders of magnitude faster than previously reported results. A classical channel at 1550 nm operates in parallel with a quantum channel at 845 nm. Clock recovery techniques on the classical channel at 1.25 Gbps enable quantum transmission at up to the clock rate. System performance is currently limited by the timing resolution of our silicon avalanche photodiode detectors. With improved detector resolution, our technique will yield another order of magnitude increase in performance, with existing technology. PMID- 19475037 TI - Dynamics of optical backward-injection-induced gain-depletion modulation and mode locking in semiconductor optical amplifier fiber lasers. AB - The optical gain-depletion-induced mode-locking dynamics of a semiconductor optical-amplifier-based fiber ring laser (SOAFL) backward injected by a purely sinusoidally modulated or digitally encoded distributedfeedback laser diode are theoretically and experimentally demonstrated. The effect of gain depletion and waveform on the mode-locked pulse width, pulse shape, and power of the SOAFL are interpreted from theoretical simulations. The shortest pulse width of 12 ps can be generated from an optically sinusoidal-wave-modulated SOAFL. By backward injecting the SOAFL with a digitally encoded optical signal of adjustable duty cycle, one can observe the optimized gain depletion time of 400-600 ps required for mode locking the SOAFL. PMID- 19475038 TI - Highly nonlinear dispersion-flattened photonic crystal fibers for supercontinuum generation in a telecommunication window. AB - We propose a new structure of highly nonlinear dispersion-flattened (HNDF) photonic crystal fiber (PCF) with nonlinear coefficient as large as 30 W(-1)km( 1) at 1.55 microm designed by varying the diameters of the air-hole rings along the fiber radius. This innovative HNDF-PCF has a unique effective-index profile that can offer not only a large nonlinear coefficient but also flat dispersion slope and low leakage losses. It is shown through numerical results that the novel microstructured optical fiber with small normal group-velocity dispersion and nearly zero dispersion slope offers the possibility of efficient supercontinuum generation in the telecommunication window using a few ps pulses. PMID- 19475039 TI - Four-wave mixing in fibers with random birefringence. AB - Parametric amplification is made possible by four-wave mixing. In low birefringence fibers the birefringence axes and strength vary randomly with distance. Light-wave propagation in such fibers is governed by the Manakov equation. In this paper the Manakov equation is used to study degenerate and nondegenerate four-wave mixing. The effects of linear and nonlinear wavenumber mismatches, and nonlinear polarization rotation, are included in the analysis. Formulas are derived for the initial quadratic growth of the idler power, and the subsequent exponential growth of the signal and idler powers (which continues until pump depletion occurs). These formulas are valid for arbitrary pump and signal polarizations. PMID- 19475040 TI - Simultaneous four-wavelength lasing oscillations in an erbium-doped fiber laser with two high birefringence fiber Bragg gratings. AB - A novel multiwavelength erbium-doped fiber laser configuration is proposed and demonstrated. The laser can produce simultaneous four-wavelength lasing oscillations with a minimum wavelength spacing of only 0.36 nm in C-band via using two fiber Bragg gratings written in high birefringence fiber, while ensuring fairly stable room-temperature operation. The laser can also achieve switching modes among four wavelengths by simple adjustment of two polarization controllers in the cavities. Theconfiguration is based on the polarization hole burning and overlapping cavities principle. The laser has the advantages of simple all-fiber configuration, low cost, high stability and operating at room temperature. PMID- 19475041 TI - Mode calculations for a terahertz quantum cascade laser. AB - We calculate the loss and confinement factors of modes in terahertz quantum cascade laser structures at frequencies of 1-4 THz. The determination of the total loss splits naturally into the calculation of free carrier losses in the active region and the waveguide losses. For both, we employ the Drude model. In the case of waveguide losses, we incorporate it into the formalism of the optical scattering matrix and trace the net threshold gain for laser operation in the waveguide for various frequencies as a function of thickness and doping of the buried contact layer. The results indicate that at lower frequencies and high doping, the preferred mode switches character from extended to tightly confined. This may have consequences for the creation of simplified longer-wavelength devices. PMID- 19475042 TI - Carrier-envelope-phase stabilized chirped-pulse amplification system scalable to higher pulse energies. AB - We have demonstrated a carrier-envelope phase (CEP) stabilized chirped-pulse amplification (CPA) system employing a grating-based pulse stretcher and compressor and a regenerative amplifier for the first time. In addition to stabilizing the carrier-envelope offset phase of a laser oscillator, a new pulse selection method referenced to the carrier-envelope offset beat signal was introduced. The pulse-selection method is more robust against the carrier envelope offset phase fluctuations than a simple pulse-clock dividing method. We observed a stable fringe in a self-referencing spectrum interferometry of the amplified pulse, which implies that the CEP of amplified pulse is stabilized. We also measured the effect of the beam angle change on the CEP of amplified pulses. The result demonstrates that the CEP stabilized CPA is scalable to higher-pulse energies. PMID- 19475043 TI - Transmission study of prisms and slabs of lossy negative index media. AB - Within an effective medium theory, we numerically study by means of a finite element method the transmission properties of prisms and slabs of media with negative refractive index. The constitutive parameters employed are similar to those of recent experiments that confirmed the existence of negative refraction as well as the focusing property of flat slabs. In this way, we further analyze in detail the influence of diffraction and scattering due to the large wavelength of the radiation in use, and its suppression by employing waveguide configurations with absorbing walls. Also, we address the effects of different amounts of absorption on both the angle of refraction, (for which we derive a new refraction law in prisms), and on the position, resolution and isoplantism of the focus produced by flat slabs. PMID- 19475044 TI - Chromatic confocal microscopy using supercontinuum light. AB - We report on a novel chromatic confocal microscope system using supercontinuum white light generated from a photonic crystal fiber. The chromatic aberration of a pair of singlet lenses is employed to focus the different spectral components of the supercontinuum at different depth levels. An effective depth scanning range of 7 microm is demonstrated. The corresponding depth resolution is measured to be less than 1 microm (FWHM). PMID- 19475045 TI - Liquid phantom for investigating light propagation through layered diffusive media. AB - A liquid phantom for investigating light propagation through layered diffusive media is described. The diffusive medium is an aqueous suspension of calibrated scatterers and absorbers. A thin membrane separates layers with different optical properties. Experiments showed that a material with scattering properties should be used for the membrane to avoid the perturbation due to the guided propagation that occurs through a transparent layer. Examples of measurements on a three layered medium are reported both in the cw and in the time domain. PMID- 19475046 TI - Ultrahigh resolution optical coherence tomography imaging with a broadband superluminescent diode light source. AB - Ultrahigh resolution optical coherence tomography imaging is performed with a compact broadband superluminescent diode light source. The source consists of two multiplexed broadband superluminescent diodes and has a power output of 4 mW with a spectral bandwidth of 155 nm, centered at a wavelength of 890 nm. In vivo imaging was performed with approximately 2.3 microm axial resolution in scattering tissue and approximately 3.2 microm axial resolution in the retina. These results demonstrate that it is possible to perform in vivo ultrahigh resolution optical coherence tomography imaging using a superluminescent diode light source that is inexpensive, compact, and easy to operate. PMID- 19475047 TI - Fabrication of high-aspect ratio, micro-fluidic channels and tunnels using femtosecond laser pulses and chemical etching. AB - We present novel results obtained in the fabrication of high-aspect ratio micro fluidic microstructures chemically etched from fused silica substrates locally exposed to femtosecond laser radiation. A volume sampling method to generate three-dimensional patterns is proposed and a systematic SEM-based analysis of the microstructure is presented. The results obtained gives new insights toward a better understanding of the femtosecond laser interaction with fused silica glass (a-SiO(2)). PMID- 19475048 TI - Stabilizing and controlling domain walls and dark-ring cavity solitons. AB - We demonstrate two alternative techniques for controlling and stabilizing domain walls (DW) in phase-sensitive, nonlinear optical resonators. The first of them uses input pumps with spatially modulated phase and can be applied also to dark ring cavity solitons. An optical memory based on the latter is demonstrated. Here the physical mechanism of control relies on the advection caused to any feature by the phase gradients. The second technique uses a plane wave input pump with holes of null intensity across its transverse plane, which are able to capture DWs. Here the physical mechanism of control is of topological nature. When distributed as a regular array, these holes delimit spatial optical bits which constitute an optical memory. These techniques are illustrated in a degenerate optical parametric oscillator model, but can be applied to any phase-sensitive nonlinear optical cavity. PMID- 19475049 TI - Variable-focus lens with 1-kHz bandwidth. AB - This paper proposes a variable-focus lens with 1-kHz bandwidth. The lens transforms its shape rapidly using the liquid pressure generated by a piezo stack actuator. This mechanism also includes a built-in motion amplifier with high bandwidth to compensate for the short working range of the piezo stack actuator. Prototypes have been developed to validate the proposed design. A 1-kHz bandwidth of the lenses was confirmed by measuring the frequency responses. Refractive power ranging from -1/167 to 1/129 mm(-1) and a maximum resolution of 12.3 cycles/mm were attained. PMID- 19475050 TI - Efficient second harmonic generation of femtosecond laser at one micron. AB - By using spectrally noncritical phase-matching in a partially deuterated KDP around its retracing point of phase-matching, we have experimentally and numerically investigated the characteristics of second-harmonic generation (SHG) with femtosecond laser at 1 microm for the first time. This phase-matching configuration can support efficient SHG over 20nm bandwidth of the fundamental laser at 1 microm in a 10-mm-long crystal. Efficiency of harmonic conversion as high as 55% has been demonstrated. PMID- 19475052 TI - Phase, timing, and amplitude noise on supercontinua generated in microstructure fiber. AB - During supercontinuum formation in nonlinear fiber the presence of a noise seed on the input laser pulse can lead to significant excess noise on the generated output supercontinuum electric field. We relate pulse-averaged moments of this electric-field noise to the measured RF spectrum of the frequency comb formed by the supercontinuum. We present quantitative numerical results for the intrinsic phase and amplitude noise on the frequency comb resulting from input shot noise, including the scaling of the noise with different experimental parameters. This intrinsic noise provides a fundamental lower limit to the phase stability of frequency combs that originate from microstructure fiber. PMID- 19475051 TI - Ultrahigh resolution Fourier domain optical coherence tomography. AB - We present, for the first time, in vivo ultrahigh resolution (~2.5 microm in tissue), high speed (10000 A-scans/second equivalent acquisition rate sustained over 160 A-scans) retinal imaging obtained with Fourier domain (FD) OCT employing a commercially available, compact (500x260mm), broad bandwidth (120 nm at full width-at-half-maximum centered at 800 nm) Titanium:sapphire laser (Femtosource Integral OCT, Femtolasers Produktions GmbH). Resolution and sampling requirements, dispersion compensation as well as dynamic range for ultrahigh resolution FD OCT are carefully analyzed. In vivo OCT sensitivity performance achieved by ultrahigh resolution FD OCT was similar to that of ultrahigh resolution time domain OCT, although employing only 2-3 times less optical power (~300 microW). Visualization of intra-retinal layers, especially the inner and outer segment of the photoreceptor layer, obtained by FDOCT was comparable to that, accomplished by ultrahigh resolution time domain OCT, despite an at least 40 times higher data acquisition speed of FD OCT. PMID- 19475053 TI - Photonic crystal characterization by FDTD and principal component analysis. AB - We demonstrate the capabilities of principal component analysis (PCA) for studying the results of finite-difference time-domain (FDTD) algorithms in simulating photonic crystal microcavities. The spatial-temporal structures provided by PCA are related to the actual electric field vibrating inside the photonic microcavity. A detailed analysis of the results has made it possible to compute the phase maps for each mode of the arrangement at their respective resonant frequencies. The existence of standing wave behavior is revealed by this analysis. In spite of this, some numerical artifacts induced by FDTD algorithms have been clearly detailed through PCA analysis. The data we have analyzed are a given set of maps of the electric field recorded during the simulation. PMID- 19475054 TI - 40 GHz adiabatic compression of a modulator based dual frequency beat signal using Raman amplification in dispersion decreasing fiber. AB - We demonstrate the use of distributed Raman amplification (DRA) in a dispersion decreasing fiber (DDF) for the efficiency enhancement of adiabatic soliton compression of a dual frequency beat signal. We compress a 40 GHz beat signal generated from a LiNbO3 modulator at a driving RF frequency of 20 GHz into ~ 2.2 ps soliton pulses using DRA in a 20 km DDF. The generation of high quality of soliton pulses from the 40 GHz sinusoidal beat signal is readily achieved with a significantly enhanced efficiency using DDF based DRA, compared to the case of using a DDF without DRA or a DSF with DRA. PMID- 19475055 TI - Colored solitons interactions: particle-like and beyond. AB - The interaction of two colored solitons was analyzed in the framework of a particle-like model, derived from a soliton perturbation theory. From "energy" considerations, a soliton capture threshold and the re-coloring of the escaping solitons were derived. The results were compared to the spectral boundaries of a second order soliton as well as to previous reports. The capture of colored solitons was shown to be impractical without additional means. This particle-like model was further generalized to apply also for non-equal intensity colored solitons. Detailed calculations-beyond the particle-like approximation, exhibited additional mechanisms, namely dissipation and friction-like forces, which served as sources for the relaxation of the solitons oscillations within the captured state, thus enhancing the capture phenomenon. PMID- 19475056 TI - Spectral phase conjugation with cross-phase modulation compensation. AB - Spectral phase conjugation with short pump pulses in a third-order nonlinear material is analyzed in depth. It is shown that if signal amplification is considered, the conversion efficiency can be significantly higher than previously considered, while the spectral phase conjugation operation remains accurate. A novel method of compensating for cross-phase modulation, the main parasitic effect, is also proposed. The validity of our theory and the performance of the spectral phase conjugation scheme are studied numerically. PMID- 19475057 TI - Rigorous time domain simulation of momentum transfer between light and microscopic particles in optical trapping. AB - Laser light can exert forces on matter by exchanging momentum in form of radiation pressure and refraction. Although these forces are small, they are sufficient to trap and manipulate microscopic particles [Phys. Rev. Lett. 24, 156 (1970)]. In this paper, we study the optical trapping phenomena by using computer simulation to show a detailed account of the process of momentum exchange between a focused light and a microscopic particle in an optical trapping by use of the finite difference time domain method. This approach provides a practical routine to predict the magnitude of the exchanged momentum, track the particle in a trapping process, and determine a trapping point, where dynamic equilibrium happens. Here we also theoretically describe the transfer procedure of orbital angular momentum from a focused optical vortex to the particle. PMID- 19475058 TI - Control of dispersion in a femtosecond ytterbium laser by use of hollow-core photonic bandgap fiber. AB - We demonstrate the use of photonic bandgap fiber for dispersion compensation in a short-pulse fiber laser. The anomalous dispersion provided by the photonic bandgap fiber enables us to construct a femtosecond fiber laser at 1 micron wavelength without prisms or diffraction gratings. The laser is self-starting and produces 160-fs pulses with 1-nJ energy, and represents a significant step toward all-fiber devices capable of much higher pulse energies. PMID- 19475059 TI - Noncollinear second-harmonic generation in sub-micrometer-poled RbTiOPO(4). AB - We have generated noncollinear quasi-phase-matched second harmonic wave in an RbTiOPO(4) crystal that was poled using the high-voltage atomic force microscope (HV-AFM). To the best of our knowledge, this is the first systematic nonlinear frequency conversion study of samples produced by the HV-AFM method. The short poling period of 1.18 microm enabled us to observe second harmonic generation at very large angles with respect to the fundamental wave. The setup was used to optically explore the homogeneity of the poled area. The measurements are in a reasonable agreement with an analytic calculations. PMID- 19475060 TI - Diffractive optical tweezers in the Fresnel regime. AB - We demonstrate a flexible setup for holographic steering of laser tweezers in microscopy using a high resolution spatial light modulator (SLM). In contrast to other methods, hologram read-out is done in the off-axis Fresnel regime rather than in the typically used on-axis Fourier regime. The diffractive structure is calculated as a Fresnel hologram, such that after reflection at the SLM only the desired first diffraction order is guided to the input of an optical microscope, where it generates a tailored optical tweezers field. We demonstrate some advantageous features of this setup, i.e. undesired diffraction orders are suppressed, the optical traps can be easily steered in real-time by just "mouse dragging" a hologram window at the SLM display, and a number of independently steerable optical traps can be generated simultaneously in a three-dimensional arrangement by displaying a corresponding number of adjacent hologram windows at the SLM screen. PMID- 19475061 TI - Recovery of a flawed hyperspectral imager calibration using optical modeling. AB - A reconstructed hyperspectral datacube has been successfully recovered from a badly flawed point-spread function (PSF) observation. The corrected PSF alleviated unnoticed detector saturation and misregistration artifacts in the calibration of a crucial, irreplaceable near-infrared flash hyperspectral imager dataset. This flawed PSF induced a defocus-like artifact as well as spectral distortions in the three-dimensional hyperspectral estimate of the data. The PSF artifacts, which would have caused severe misinterpretation of the spatio spectral information, were correctable post detection using an optical model of the PSF constrained by the available flawed calibration. PMID- 19475062 TI - Ultra-low-loss optical fiber nanotapers. AB - Optical fiber tapers with a waist size larger than 1microm are commonplace in telecommunications and sensor applications. However the fabrication of low-loss optical fiber tapers with subwavelength diameters was previously thought to be impractical due to difficulties associated with control of the surface roughness and diameter uniformity. In this paper we show that very-long ultra-low-loss tapers can in fact be produced using a conventional fiber taper rig incorporating a simple burner configuration. For single-mode operation, the optical losses we achieve at 1.55microm are one order of magnitude lower than losses previously reported in the literature for tapers of a similar size. SEM images confirm excellent taper uniformity. We believe that these low-loss structures should pave the way to a whole range of fiber nanodevices. PMID- 19475063 TI - Planar waveguide lasers by proton implantation in Nd:YAG crystals. AB - The performance of CW Nd:YAG waveguide lasers operating at 1.06 microm at room temperature is described. The waveguides were fabricated by proton implantation and the main differences in the process of fabrication were the angle of implantation and the total dose implanted. The characterization of the waveguide refractive index profile induced by proton implantation and the main laser characteristics i.e., slope efficiency and threshold are presented. PMID- 19475064 TI - Digital in-line holography: influence of the shadow density on particle field extraction. AB - We have used a digital in-line holography system with numerical reconstruction for 3D particle field extraction. In this system the diffraction patterns (holograms) are directly recorded on a charge-coupled device (CCD) camera. The numerical reconstruction is based on the wavelet transformation method. A sample volume is reconstructed by computing the wavelet components for different scale parameters. These parameters are related to the axial distance between a particle and the CCD camera. The particle images are identified and localized by analyzing the maximum of the wavelet transform modulus and the equivalent diameter of the particle image. The general process for the 3D particle location and data processing method are presented. As in classical holography we found that the signal to noise ratio depends only on the shadow density. Nevertheless, we show that both the volume depth and the shadow density affect the percentage of extracted particles. PMID- 19475065 TI - Polarisation and wavelength division multiplexing at 1.55 mum for bandwidth enhancement of multimode fibre based access networks. AB - We demonstrate how a combination of polarisation-division multiplexing (PDM) and wavelength-division multiplexing (WDM) applied to graded index 50 mum multimode fibres (MMF) at 1.55 mum can be used to greatly increase the available optical bandwidth. A proof of principle experiment demonstrated error-free data transmission over 3km of MMF, using two 100GHz-spaced wavelengths, each carrying two 2.5Gb/s orthogonal PDM multiplexed channels, resulting in a 10Gb/s data rate. Polarisation and wavelength demultiplexing were simultaneously achieved by use of a grating based monochromator. We also practically implemented this transmission scheme in an all-fibre experiment, replacing the monochromator by a more convenient polarisation-insensitive, 200GHz ITU grid spacing 62.5 mum MMF pigtailed WDM demultiplexer. Using two polarizations each on four wavelengths (2P x 4lambda), we repeatedly achieved error-free data transmission for both circularly and linearly polarisation-wavelength-division-multiplexed channels over a MMF span of 300m, featuring a 20Gb/s data rate. Overall, we have demonstrated a major increase in the MMF bandwidth-distance product up to 30GHz km. PMID- 19475066 TI - Oscillation spectra and dynamic effects in a highly-doped microchip Nd:YAG ceramic laser. AB - This work reports on a beam quality and dynamic behaviors of a mirror-coated highly-doped YAG (Y(3)Al(5)O(12)) microchip ceramic laser possessing an increased number of grain boundaries. The degradation of beam quality factor in transverse patterns due to spatial inhomogeneity across the beam, multiple split-mode operations, violation of antiphase dynamics and high-speed intensity modulations due to the interference between non-orthogonal transverse modes were observed in a laser-diode end-pumping scheme. PMID- 19475067 TI - Optical fiber microcoil resonators. AB - The optical microfiber coil resonator with self-coupling turns is suggested and investigated theoretically. This type of a microresonator has a three-dimensional geometry and complements the well-known Fabry-Perot (one-dimensional geometry, standing wave) and ring (two-dimensional geometry, traveling wave) types of microresonators. The coupled wave equations for the light propagation along the adiabatically bent coiled microfiber are derived. The particular cases of a microcoil having two and three turns are considered. The effect of microfiber radius variation on the value of Q-factor of resonances is studied. PMID- 19475068 TI - Efficient selection of focusing optics in non linear microscopy design through THG analysis. AB - A theoretical and experimental study of the THG signal from a reference interface in confocal microscope allows precise analysis of beam propagation and optimization of the focusing objectives. PMID- 19475069 TI - Joint routing-selection algorithm for a shared path with differentiated reliability in survivable wavelength-division-multiplexing mesh networks. AB - A routing-selection algorithm is important in survivable wavelength-division networks. A sound algorithm should carefully consider the efficiency of resource utilization and the protection-switching time. Under shared-risk link group constraints with differentiated reliability (DiR), a novel algorithm for a shared path, called a joint routing-selection algorithm (JRSA) with DiR, is proposed. The simulation results show that a JRSA with DiR not only can efficiently satisfy the specific requirements of users but also can produce nearly optimal performance and determine the appropriatetrade-offs between the resource utilization ratio and the protection-switching time. PMID- 19475070 TI - Photonic crystal to photonic crystal surface modes: narrow-bandpass filters. AB - The properties of surface modes present in the junction of two different one dimensional photonic crystals placed in series are studied to assess the possibility of applying them in the design of narrow-bandpass filters. To design bandpass filters that are similar in many respects to multiple-cavity Fabry-Perot filters, we also consider the coupling conditions for these surface modes for multiple photonic crystals placed in series to form a multiple-junction system. PMID- 19475071 TI - New ring resonator configuration using hybrid photonic crystal and conventional waveguide structures. AB - We propose a new method of realizing ring resonators based on hybrid photonic crystal and conventional waveguide structures. The proposed ring resonator configuration is advantageous compared with general ring resonator structures for its controllability of the quality (Q) factor, free spectral range (FSR), and full width at half maximum (FWHM) over a wide range. We show ring resonator structures based on a single mode waveguide with core and clad refractive indices of 1.5 and 1.465, respectively. A 35mum x 50mum ring resonator has a free spectral range (FSR) of 14.1nm and a quality (Q) factor of 595 with high optical efficiency (92.7%). By decreasing the size of the ring resonator to 35mum x 35mum, the FSR is increased to 19.8nm. Modifying the splitting ratio of the beam splitters permits the Q factor to be increased to 1600. PMID- 19475072 TI - A birefringent etalon as single-mode selector in a laser cavity. AB - A novel technique is demonstrated for stabilizing an intra-cavity etalon used for single-mode selection in a laser cavity. By appropriate polarization analysis of the reflection from an etalon designed as a quarterwave plate an electronic signal can be derived, that enables the implementation of an electronic stabilization scheme. This scheme obviates the need for any modulation of the etalon in order to ensure stable single mode operation of a cw tunable laser. PMID- 19475073 TI - Photonic crystal fibers with squeezed hexagonal lattice. AB - We study the birefringence and polarization coupling in the index-guiding photonic crystal fibers (PCFs) with squeezed hexagonal crystal lattice. The sign of form birefringence in such photonic crystal fibers can be changed as the wavelength changes, which is reported for the first time to our knowledge. A PCF based polarization splitter with squeezed hexagonal lattice is proposed to achieve excellent extinction ratio and a simpler structure than those reported previously. PMID- 19475074 TI - Detection of neural activity using phase-sensitive optical low-coherence reflectometry. AB - We demonstrate non-contact sub-nanometer optical measurement of neural surface displacement associated with action potential propagation. Experimental results are recorded from nerve bundles dissected from crayfish walking leg using a phase sensitive optical low coherence reflectometer. No exogenous chemicals or reflection coatings are applied. Transient neural surface displacement is less than 1 nm in amplitude, 1 ms in duration and is coincident with action potential arrival to the optical measurement site. Because the technique uses back reflected light, noninvasive detection of various neuropathies may be possible. PMID- 19475075 TI - Direct Visualization of a Polariton Resonator in the THz Regime. AB - We report fabrication of a THz phonon-polariton resonator in a single crystal of LiNbO3 using femtosecond laser machining with high energy pulses. Fundamental and overtone resonator modes are excited selectively and monitored through spatiotemporal imaging. The resonator is integrated into a single solid-state platform that can include THz generation, manipulation, readout and other functionalities. PMID- 19475076 TI - Optical parametric chirped pulse amplification and spectral shaping of a continuum generated in a photonic band gap fiber. AB - A chirped pulse, spectrally broadened in a photonic bandgap optical fiber by 120 fs Ti:Sapphire laser pulses, is parametrically amplified in a BBO crystal pumped by a frequency doubled nanosecond Nd:YAG laser pulse. Without changing the frequency of the Ti:Sapphire, a spectral tunability of the amplified pulses is demonstrated. The possibility to achieve broader spectral range amplification is confirmed for a non-collinear pump-signal interaction geometry. For optimal non collinear interaction geometry, the pulse duration of the original and amplified pulse are similar. Finally, we demonstrate that the combination of two BBO crystals makes it possible to spectrally shape the amplified pulses. PMID- 19475077 TI - Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation. AB - Ultrahigh-resolution optical coherence tomography uses broadband light sources to achieve axial image resolutions on the few micron scale. Fourier domain detection methods enable more than an order of magnitude increase in imaging speed and sensitivity, thus overcoming the sensitivity limitations inherent in ultrahigh resolution OCT using standard time domain detection. Fourier domain methods also provide direct access to the spectrum of the optical signal. This enables automatic numerical dispersion compensation, a key factor in achieving ultrahigh image resolutions. We present ultrahigh-resolution, high-speed Fourier domain OCT imaging with an axial resolution of 2.1 im in tissue and 16,000 axial scans per second at 1024 pixels per axial scan. Ultrahigh-resolution spectral domain OCT is shown to provide a ~100x increase in imaging speed when compared to ultrahigh resolution time domain OCT. In vivo imaging of the human retina is demonstrated. We also present a general technique for automatic numerical dispersion compensation, which is applicable to spectral domain as well as swept source embodiments of Fourier domain OCT. PMID- 19475078 TI - Fundamental limits to few-cycle pulse generation from compression of supercontinuum spectra generated in photonic crystal fiber. AB - The fundamental limits to the compressibility of broadband supercontinuum spectra generated in photonic crystal fiber are examined using numerical simulations based on a stochastic extended nonlinear Schrodinger equation. An ensemble average over multiple simulations performed with random quantum noise on the input pulse and spontaneous Raman noise during propagation allows a quantitative study of the effects of pulse to pulse fluctuations on the ability to obtain few cycle pulses after compensation of the supercontinuum spectral phase. We study the dependence of the supercontinuum compressibility on the input pulse duration, the photonic crystal fiber length, and the spectral resolution of the pulse compressor employed. PMID- 19475079 TI - Broadband emission in Er(3+)-Tm(3+) codoped tellurite fibre. AB - The visible and near infrared emission spectra of Er(3+)-Tm3(3+)-codoped tellurite glasses and fibres were measured with the excitation of an 800 nm laser. A broad emission extending from 1.35 mum to 1.6 mum with a full width at half-maximum (FWHM) of ~160 nm was recorded in a 24 cm long 0.2 wt% Er(2)O(3) and 1.0 wt% Tm(2)O(3) codoped tellurite fibre. Energy transfer between Er(3+) and Tm(3+) play important roles in the luminescence mechanism. These results indicate that Er(3+)-Tm(3+) codoped tellurite fibre could be a promising material for broadband light source and broadband amplifier for the wavelength-division multiplexing (WDM) transmission systems. PMID- 19475080 TI - Ultrahigh-resolution high-speed retinal imaging using spectral-domain optical coherence tomography. AB - We present the first ultrahigh-resolution optical coherence tomography (OCT) structural intensity images and movies of the human retina in vivo at 29.3 frames per second with 500 A-lines per frame. Data was acquired at a continuous rate of 29,300 spectra per second with a 98% duty cycle. Two consecutive spectra were coherently summed to improve sensitivity, resulting in an effective rate of 14,600 A-lines per second at an effective integration time of 68 micros. The turn key source was a combination of two super luminescent diodes with a combined spectral width of more than 150 nm providing 4.5 mW of power. The spectrometer of the spectraldomain OCT (SD-OCT) setup was centered around 885 nm with a bandwidth of 145 nm. The effective bandwidth in the eye was limited to approximately 100 nm due to increased absorption of wavelengths above 920 nm in the vitreous. Comparing the performance of our ultrahighresolution SD-OCT system with a conventional high-resolution time domain OCT system, the A-line rate of the spectral-domain OCT system was 59 times higher at a 5.4 dB lower sensitivity. With use of a software based dispersion compensation scheme, coherence length broadening due to dispersion mismatch between sample and reference arms was minimized. The coherence length measured from a mirror in air was equal to 4.0 microm (n= 1). The coherence length determined from the specular reflection of the foveal umbo in vivo in a healthy human eye was equal to 3.5 microm (n = 1.38). With this new system, two layers at the location of the retinal pigmented epithelium seem to be present, as well as small features in the inner and outer plexiform layers, which are believed to be small blood vessels. ?2004 Optical Society of America. PMID- 19475082 TI - Synthetic phase holograms for auto-stereoscopic image displays using a modified IFTA. AB - A Fourier-transformed synthetic phase hologram for an auto-stereoscopic image display system is proposed and implemented. The system uses a phase-only spatial light modulator and a simple projection lens module. A modified iterative Fresnel transform algorithm method, for the reconstruction of gray-level quantized stereo images with fast convergence, high diffraction efficiency and large signal-to noise ratio is also described. Using this method, it is possible to obtain a high diffraction efficiency(~90%), an excellent signal-to-noise ratio(> 9.6dB), and a short calculation time(~3min). Experimentally, the proposed auto-stereoscopic display system was able to generate stereoscopic 3D images very well. PMID- 19475081 TI - Sub-picosecond pulse generation employing an SOA-based nonlinear polarization switch in a ring cavity. AB - We demonstrate the generation of sub-picosecond optical pulses using a semiconductor optical amplifier (SOA) and a linear polarizer placed in a ring laser configuration. Nonlinear polarization rotation in the SOA serves as the passive mode-locking mechanism. The ring cavity generates pulses with duration below 800 fs (FWHM) at a repetition rate of 14 MHz. The time -bandwidth product is 0.48. Simulation results in good agreement with the experimental results are presented. PMID- 19475083 TI - New approach for the radiometric calibration of spectral imaging systems. AB - The calibration of multispectral and hyperspectral imaging systems is typically done in the laboratory using an integrating sphere, which usually produces a signal that is red rich. Using such a source to calibrate environmental monitoring systems presents some difficulties. Not only is much of the calibration data outside the range and spectral quality of data values that are expected to be captured in the field, using these measurements alone may exaggerate the optical flaws found within the system. Left unaccounted for, these flaws will become embedded in to the calibration, and thus, they will be passed on to the field data when the calibration is applied. To address these issues, we used a series of well-characterized spectral filters within our calibration. It provided us with a set us stable spectral standards to test and account for inadequacies in the spectral and radiometric integrity of the optical imager. PMID- 19475084 TI - In vivo multimodal nonlinear optical imaging of mucosal tissue. AB - We present a multimodal nonlinear imaging approach to elucidate microstructures and spectroscopic features of oral mucosa and submucosa in vivo. The hamster buccal pouch was imaged using 3-D high resolution multiphoton and second harmonic generation microscopy. The multimodal imaging approach enables colocalization and differentiation of prominent known spectroscopic and structural features such as keratin, epithelial cells, and submucosal collagen at various depths in tissue. Visualization of cellular morphology and epithelial thickness are in excellent agreement with histological observations. These results suggest that multimodal nonlinear optical microscopy can be an effective tool for studying the physiology and pathology of mucosal tissue. PMID- 19475085 TI - Color computer-generated holograms from projection images. AB - A novel method for the procurement of full-color three-dimensional (3-D) images of real objects has been developed. This method is based on extracting information from 3-D Fourier spectra, which are calculated from several projection images recorded using a white light source. 3-D Fourier spectra for three colors were obtained separately for projection images recorded with a color CCD camera. Three computer-generated holograms (CGHs) were then synthesized from those Fourier spectra. The resulting numerically and optically reconstructed full color images are presented. PMID- 19475086 TI - Tunable microdoublet lens array. AB - We report a tunable microdoublet lens capable of creating dual modes of biconvex or meniscus lens. The microdoublet lens consists of a tunable liquid-filled lens and a solid negative lens. It can be tuned either by changing the shape of the liquid-filled lens into bi-convex or meniscus or by changing a filling media with different refractive index. The micro-fabrication is based on photopolymer microdispensing and elastomer micromolding methods. The microdoublet lens can provide a solution for minimizing optical aberrations and maximizing the tunability of focal length or field of view by controlling variable and fixed lens curvatures. PMID- 19475087 TI - Deposition and characterization of germanium sulphide glass planar waveguides. AB - Germanium sulphide glass thin films have been deposited on CaF2 and Schott N PSK58 glass substrates directly by means of chemical vapor deposition (CVD). The deposition rate of germanium sulphide glass film by this CVD process is estimated about 12 microm/hr at 500oC. These films have been characterized by micro-Raman spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Their transmission range extends from 0.5microm to 7microm measured by UV-VIS-NIR and FT-IR spectroscopy. The refractive index of germanium sulphide glass film measured by prism coupling technique was 2.093+/-0.008 and the waveguide loss measured at 632.8nm by He-Ne laser was 2.1+/-0.3 dB/cm. PMID- 19475088 TI - New bit-error-rate monitoring technique based on histograms and curve fitting. AB - We propose a new method for estimating the bit error rate (BER) of optical channels suffering from crosstalk and waveform distortion. We demonstrate experimentally that the new method can provide a good BER estimation with an error range less than one order of magnitude. PMID- 19475089 TI - Low-coherence interference microscopy using a ferro-electric liquid crystal phase modulator. AB - We describe a computer-controlled low-coherence interference microscope, based on a Linnik interferometer configuration that can rapidly and accurately map the shape of micro-machined surfaces exhibiting steps and discontinuities. The novel feature of the system is a fast, switchable achromatic phase-modulator operating on the geometric phase, using a pair of ferro-electric liquid crystal devices. PMID- 19475090 TI - Dynamic correction of a distorted image using a photorefractive polymeric composite. AB - We demonstrate, for the first time, the dynamic correction of aberrated images in real-time using a polymeric composite with fast response times. The current novel experimental design is capable of restoring a phase aberrated, image carrying laser beam, to nearly its original quality. The ability to reconstruct images in real-time is demonstrated through the changing of the aberrating medium at various speeds. In addition, this technique allows for the correction of images in motion, demonstrated through the oscillatory movement of the resolution target. We also have demonstrated that important parameters of the materials in the study such as response times, diffraction efficiencies and optical gains all retain high figures of merit values under the current experimental conditions. PMID- 19475091 TI - Grating pseudo-imaging with polychromatic and finite extension sources. AB - The pseudo-imaging process in a system consisting of two periodic gratings and illuminated by an incoherent polychromatic and finite extension source placed at a finite distance from the gratings is studied. An analytical expression of the irradiance distribution on a plane, also located at a finite distance from the gratings, has been obtained from previous results on monochromatic illumination. In the analysis presented, different imaging regimes are found and related to the parameters which characterize the double grating system. The pseudo-imaging phenomenon strongly depends on both the spatial and temporal coherence of the incident illuminating field. Certain pseudo-images are observed with polychromatic and incoherent incident light under some restrictions. On the other hand, pseudo-image process analogous to Talbot effect appears only by monochromatic and plane illuminating wavefront. PMID- 19475092 TI - Evaluation scheme for the design of poweroptimized single mode vertical-cavity surfaceemitting lasers. AB - A very simple and efficient evaluation procedure is suggested for the design of power-optimized single mode VCSELs by reviewing the physical mechanisms that governs mode transition and simplifying the computation steps. In addition, the new structures are proposed and tested following the suggested evaluation procedure. As a result, the proposed design exhibits much better stability of the fundamental mode over a current range wider than the conventional one. PMID- 19475093 TI - Symmetry properties with pupil phase-filters. AB - Pupil filters can modify the three dimensional response of an optical system. In this paper, we study different pupil symmetries that produce a predictable image behavior. We show that different pupil-filters that satisfy certain symmetry conditions can produce axial responses which are either identical or mirror reflected. We also establish the differences in the symmetry properties between amplitude-only filters and phase-only filters. In particular, we are interested in phase filters that produce transverse superresolution with axial superresolution or high depth of focus. PMID- 19475094 TI - Optical guiding of microscopic particles in femtosecond and continuous wave Bessel light beams. AB - Optical guiding of microscopic particles is studied and compared for femtosecond and continuous wave Bessel light beams. We confirm that optical guiding is an average power effect and observe no difference in the guiding velocities for non fluorescing polymer microspheres. Additionally, we observe second harmonic generation of guided KTP particles. This observation opens up the prospect for optical identification of guided cells for sorting purposes. PMID- 19475095 TI - Weak-wave advancement in nearly collinear four-wave mixing: comment. AB - The exponential gain predicted in "Weak-wave advancement in nearly collinear four wave mixing" [Opt. Express 10, 581 (2002)], disappears when all interacting sidebands are properly taken into account. The demonstration closely follows well established literature in the formally equivalent temporal domain. PMID- 19475096 TI - Effects of parasitic modes in high-speed LiNbO(3) optical modulators. AB - The characteristics of RF parasitic modes and the methods to suppress leakage phenomena in LiNbO(3) optical modulators were studied. The high frequency RF power transmission characteristics were simulated and experimented in the respects of LiNbO(3) wafer thickness, the kind of material contacting the back surface of the modulator chip, the gap and width of the CPW (co-planar waveguide) electrodes. An appropriate RF electrode geometry, to minimize coupling efficiency between co-planar waveguide and substrate mode, is proposed. Experimental results prove that the approaches made in this work are effective for broadening of modulation bandwidth. PMID- 19475097 TI - Application of the Alvarez-Humphrey concept to the design of a miniaturized scanning microscope. AB - This paper contains two optical designs that utilize the Alvarez- Humphrey surfaces to provide the miniature multi-modal microscope (4M device) with the additional capability of imaging different object depths onto the same image plane. The Alvarez-Humphrey surfaces are a pair of conjugate, rotationally asymmetrical, aspheric surfaces such that, the lateral movement of these surfaces across the optical axis, results in an element of variable optical power. The first design is a direct application of the Alvarez-Humphrey concept to the 4M device. However, due to the inadequate imaging performance and unavailability of space for the actuator due to proximity of the Alvarez Plates, a second design was created. The Separated Alvarez Plate Design is a unique design involving two conjugate pairs of Alvarez-Humphrey surfaces. The lateral movement of the central element changes the optical power. However, due to the symmetry of the system and the incorporation of the theoretical work done on induced aberration correction, this system has far superior performance. It also has adequate space for the actuator due to the separation of the elements. PMID- 19475098 TI - Single-step superresolution by interferometric imaging. AB - The use of vertical-cavity surface-emitting laser (VCSEL) arrays for implementation of incoherent source superresolution is presented. The method uses an interferometer setup to obtain superresolution in a single step. The novelty of the method relies on the use of a VCSEL array as the light source, which provides a set of coherent sources which are mutually incoherent. The technique accomplishes the transmission of several spatial frequency bands of the object's spectrum in parallel by use of spatial multiplexing that occurs because of the tilted illumination of the source array. The recording process is done by interference of each frequency band with a complementary set of reference plane waves. After the reconstruction process, the resolution of any optical system can approach the natural lambda/2 limit. The benefit of our system is improved modulation speed and hence more rapid image synthesis. Moreover, any desired synthetic coherent transfer function can be realized at ultrafast rates if we simply change the electrical drive of the VCSEL array. PMID- 19475099 TI - Polarization Bloch waves in photonic crystals based on vertical cavity surface emitting laser arrays. AB - The vectorial model of two-dimensional photonic crystals based on coherently coupled arrays of Vertical Cavity Surface - Emitting Lasers (VCSELs) is proposed in non-Hermitian Hamiltonian eigenproblem formulation. The polarization modes of square-symmetry photonic lattices are investigated theoretically. Rich mode structure with complimentary patterns of intensity for orthogonal polarizations of electromagnetic Bloch wave is predicted. The predicted near-field patterns of the polarization modes are confirmed in measurements of InGaAs/AlGaAs VCSEL arrays emitting at 965nm wavelength. PMID- 19475100 TI - Finite-difference time-domain analysis of self-focusing in a nonlinear Kerr film. AB - By using a finite-difference time-domain method, we analyze self-focusing effects in a nonlinear Kerr film and demonstrate that the near-field intensity distribution at the film surface can reach a stable state at only a few hundred femtoseconds after the incidence of the beam. Our simulations also show that the formation of multiple filamentations in the near-field is quite sensitive to the thickness of the nonlinear film and the power of the laser beam, strongly indicating the existence of nonlinear Fabry-Perot interference effects of the linearly polarized incident light. PMID- 19475101 TI - Random target method for fast MTF inspection. AB - A random target method for fast MTF inspection is proposed. The setup includes a random target, lens under test and a CCD camera with focus adjustment. The target consists of a random black and white pattern of a flat spectrum. The MTF of the lens is acquired by imaging the random target on the CCD using the lens under test, and then analyzing the spatial frequency content of the image. Frequency range up to about 50 cycles/mm is possible using commonly available CCD imagers. Measurement speed and precision depend on the sample matrix size used in calculation. A matrix of 128*128 samples per measured field point provides better than 2% precision and a few second's total execution time (ordinary PC-computer) per lens including best focus evaluation and the measurement of tangential and sagittal MTF curves of 5 field points. Thus fast MTF inspection of low to medium quality lenses seems possible. PMID- 19475102 TI - Tunable photonic-crystal waveguide Mach-Zehnder interferometer achieved by nematic liquid-crystal phase modulation. AB - Photonic crystals (PCs) have many potential applications because of their ability to control light-wave propagation and because PC-based waveguides may be integrated into optical interferometers. We propose a novel tunable PC waveguide Mach-Zehnder interferometer based on nematic liquid crystals and investigate its interference properties numerically by using the finite-difference time-domain method. We can change the refractive indices of liquid crystals by rotating the directors of the liquid crystals. Then we can control the phase of light propagation in a PC waveguide Mach-Zehnder interferometer. The interference mechanism is a change in the refractive indices of liquid-crystal waveguides. The novel interferometer can be used either as an optically controlled on-off switch or as an amplitude modulator in optical circuits. PMID- 19475103 TI - Magnetically tunable room-temperature 2 pi liquid crystal terahertz phase shifter. AB - Tunable phase shift up to 360 degrees at 1 THz is achieved with a liquid crystal (LC) device. The key to this design is (1) the use of a nematic LC, E7, which exhibits a birefringence of ~ 0.17 (0.2 - 1.2 THz); (2) a LC cell (3-mm in thickness) with sandwiched structure to increase the interaction length while minimizing interface Fresnel losses; and (3) the use of magnetic field to align the thick LC cell and achieve continuous tuning of phase from 0 to 360 degrees . This device can be operated over a broad range near room temperature. PMID- 19475104 TI - Transmission of light through small elliptical apertures. AB - The results of computer simulations based on the Finite Difference Time Domain method with local space and time grid refinement, are presented for an elliptical aperture in a thin metal film illuminated by a normally incident, monochromatic plane wave. Both cases of incident polarization parallel and perpendicular to the long axis of the ellipse are considered. An intuitive description of the behavior of the electromagnetic fields is developed in each case, and simulation results that exhibit patterns similar to those expected from this qualitative analysis are presented. The simulations reveal, in quantitative detail, the amplitude and phase behavior of the E- and B-fields in and around the aperture. PMID- 19475105 TI - Channel-selective wavelength conversion and tuning in periodically poled Ti:LiNbO(3) waveguides. AB - All-optical wavelength-selective single- and dual-channel wavelength conversion and tuning has been demonstrated in a periodically poled Ti:LiNbO(3) waveguide that has two second-harmonic phase-matching peaks by cascaded sum and difference frequency generation (cSFG/DFG). The wavelength conversion efficiency was measured to be -7 dB with coupled pump power of 233 mW. PMID- 19475106 TI - Signal to noise and range enhancement of the Brillouin intensity based temperature sensor. AB - We report on the theory and use of pre-amplification to enhance the measurement range of a spontaneous Brillouin intensity based distributed fiber-optic sensor. One factor that limits temperature resolution is receiver sensitivity, which degrades for long range sensors. Using optical preamplification before photo detection in a 23km sensor improved the signal-to-noise by approximately 17dB using a 20MHz detector. The major source of noise was amplified spontaneous emission beat noise. PMID- 19475108 TI - Exact radiation trapping force calculation based on vectorial diffraction theory. AB - There has been an interest to understand the trapping performance produced by a laser beam with a complex wavefront structure because the current methods for calculating trapping force ignore the effect of diffraction by a vectorial electromagnetic wave. In this letter, we present a method for determining radiation trapping force on a micro-particle, based on the vectorial diffraction theory and the Maxwell stress tensor approach. This exact method enables one to deal with not only complex apodization, phase, and polarization structures of trapping laser beams but also the effect of spherical aberration present in the trapping system. PMID- 19475107 TI - Characterization of a bit-wise volumetric storage medium for a space environment. AB - We report playback performance results of volumetric optical data storage disks that are made from a class of light-absorbing (photo-chromic) compounds. The disks are exposed to a simulated space environment with respect to temperature and radiation. To test for temperature sensitivity, a vacuum oven bakes the disks for certain amount of time at a designated temperature. Radiation exposure includes heavy ions and high energy protons. Disks fail in high temperature and large proton-dose conditions. Heavy ions do not cause significant disk failure. The prevention of disk failure due to harsh space environments is also discussed. PMID- 19475109 TI - Reduction of group delay ripple of multi-channel chirped fiber gratings using adiabatic UV correction. AB - We demonstrate reduction of group delay ripple (GDR) from 24 ps to 9 ps peak to peak in a four channel 43 Gb/s dispersion compensating chirped fiber grating by adiabatic UV post processing. The eye opening penalty due to the grating GDR was improved from ~2dB to <1dB for all of the channels over a range of carrier frequencies of 15GHz. Our results demonstrate that at 43 Gb/s, the adiabatic UV correction technique is sufficient to substantially improve multi-channel fiber grating performance. We also discuss three limitations of the correction technique which cause GDR to vary from channel to channel: Noise in the sampling function, cladding mode loss, and varying channel reflectivity. While these limitations are visible in our results they do not reduce the effectiveness of the adiabatic correction for our gratings. PMID- 19475110 TI - Analysis of ring-structured Bragg fibres for single TE mode guidance. AB - Ring-structured Bragg fibres that support a single TE-polarisation mode are investigated. The fibre designs consist of a hollow core and rings of holes concentric with the core, which form the low-index layers of the Bragg reflector in the cladding. The effects of varying the air fraction in each ring of holes on the transmission properties of the fibres are analysed and an approximate model based on homogenisation is explored. Surface modes and transitions thereof are also discussed. PMID- 19475111 TI - Ultrashort pulse propagation in grating-assisted codirectional couplers. AB - Ultrashort pulse propagation through grating-assisted codirectional couplers (GACCs) operating in the linear regime is theoretically investigated. For this purpose, the temporal responses of uniform GACCs to ultrashort optical pulses are calculated and the effects of varying the different physical grating parameters (e.g., length and coupling strength) on these temporal responses are evaluated. We will show that the most interesting pulse reshaping operations occur typically for the "energy receptor" mode and that depending on the length and coupling strength of the uniform perturbation one can achieve very different temporal shapes at the output of the device, including triangular pulses, square temporal waveforms as well as sequences of equalized multiple pulses. Moreover, the temporal scales of the pulses generated from a GACC are generally much shorter (in more than one order of magnitude) than those that can be generated from an equivalent Bragg grating (with the same grating length). PMID- 19475112 TI - Integrated ARROW waveguides with hollow cores. AB - We report the design, fabrication, and demonstration of antiresonant reflecting optical (ARROW) waveguides with hollow cores. We describe the design principles to achieve low waveguide loss in both transverse and lateral directions. A novel fabrication process using silicon dioxide and silicon nitride layers as well as sacrificial polyimide core layers was developed. Optical characterization of 3.5mum thick waveguides with air cores was carried out. We demonstrate single mode propagation through these hollow ARROW waveguides with propagation loss as low as 6.5cm-1 and mode cross sections down to 6.7mum2. Applications of these waveguides to sensing and quantum communication are discussed. PMID- 19475113 TI - MMI devices with weak guiding designed in three dimensions using a genetic algorithm. AB - We discuss the design of weakly guided multimode interference (MMI) devices using a genetic algorithm. For devices exhibiting a nonnegligible vertical waveguide offset, such as those produced using ion exchange in glass, three-dimensional modeling is required to properly evaluate the device performance. A combination of semivectorial finite difference modeling in two transverse dimensions and mode propagation analysis (MPA) in the propagation direction is used to evaluate the merit of each trial design. An example is provided of a 1 x 4 power splitter designed for ion exchange, which shows considerable improvement over that obtained by self-imaging theory. PMID- 19475114 TI - Requirements for the sampling source in coherent linear sampling. AB - Complex envelope measurement using coherent linear optical sampling with mode locked sources is investigated. It is shown that reliable measurement of the phase requires that one of the optical modes of the mode-locked laser be locked to the optical carrier of the data signal to be measured. Carrier-envelope offset (CEO) is found to have negligible effect on the measurement. Measurement errors of the intensity profile and phase depend on the pulsewidth and chirp of the sampling pulses as well as the detuning between the carrier frequencies of the data signal and the center frequency of sampling source. PMID- 19475115 TI - Possibility of self-similar pulse evolution in a Ti:sapphire laser. AB - A theoretical investigation of the possibility of achieving self-similar pulse propagation in a solid-state laser is presented. Limited group-velocity dispersion hinders true self-similar pulse evolution, but an intermediate regime that exhibits some of the characteristic features (and offers some of the benefits) of self-similar propagation can be reached. This regime of operation offers the potential to increase the pulse energy by at least an order of magnitude compared to energies obtained in the usual operation of Kerr-lens mode locked lasers with anomalous dispersion. Ti:sapphire lasers that generate pulse energies as high as one microjoule and peak powers of ~100 MW should be possible based on this mode of operation. PMID- 19475116 TI - Interferometric second harmonic generation microscopy. AB - We describe a novel second harmonic generation (SHG) microscope that employs heterodyne detection by interfering the epi directed SHG from a sample with SHG from a reference crystal. In addition, the microscope provides complementary reflectance information based on optical coherence microscopy (OCM). The instrument features dual balanced detection to minimize the effect of source fluctuations, and polarization-sensitive detection to measure the nonlinear susceptibility of the sample. Interferometric detection can potentially improve the sensitivity and thus extend the imaging depth as compared with direct detection of SHG. PMID- 19475117 TI - Optical binding between dielectric particles. AB - We report observation of optical binding between two dielectric particles with dimensions less than the wavelength of the interacting light. The observed dependence of the separation of optically bound Rayleigh particles on the polarization of the trapping beam is in agreement with earlier theoretical predictions. PMID- 19475118 TI - Reverse-proton-exchange in stoichiometric lithium tantalate. AB - Buried waveguides with nearly symmetrical refractive index profile and high homogeneity were obtained by applying the reverse-proton-exchange technique to MgO doped stoichiometric lithium tantalate, a promising nonlinear material due to its low coercive field and high damage threshold. By characterizing several samples fabricated under different experimental conditions, we identified a fabrication procedure in which the annealing and the reverse-exchange processes are performed at the same temperature, and the diffusion of hydrogen ions towards the substrate is negligible during the burial step. These fabrication conditions are simpler than the conventional ones used for lithium niobate. Accurate empirical laws were found, relating the fabrication conditions to the optical parameters. PMID- 19475119 TI - Experimental and theoretical demonstration of validity and limitations in fringe resolved autocorrelation measurements for pulses of few optical cycles. AB - Using 3.6- and 5.3-fs pulses, we demonstrated theoretically and experimentally that fringe-resolved autocorrelation (FRAC) traces are distorted by bandwidth limitations of the second-harmonic generation (SHG) in 10-microm-thick, type I ss BaB2O4 for pulses shorter than sub-5 fs. In addition, detailed numerical analysis of the SHG showed that the optimum crystal angle where the FRAC trace distortion becomes minimum is in disagreement not only with the phase-matching angle but also with the angle where the FRAC signal intensity becomes maximum. Furthermore, the apparent pulse duration measured at a nonoptimum angle was confirmed to become shorter than that of its transform-limited pulse, in excellent agreement with the calculated result. PMID- 19475120 TI - Influence of nonlinear absorption on Raman amplification in Silicon waveguides. AB - We model the TPA-induced free carrier absorption effect in silicon Raman amplifiers and quantify the conditions under which net gain may be obtained. The achievable Raman gain strongly depends on the free carrier lifetime, propagation loss, and on the effective Raman gain coefficient, through pump-induced broadening. PMID- 19475121 TI - High-definition real-time depth-mapping TV camera: HDTV Axi-Vision Camera. AB - We have developed a field-worthy, high-definition, real-time depth-mapping television camera called the HDTV Axi-Vision Camera. The camera can simultaneously capture both an ordinary HDTV color image and a depth image of objects on more than 1280 x 720 pixels at a frame rate of 29.97 Hz, or on 853 x 480 pixels at a frame rate of 59.94 Hz. The number of detectable pixels per unit time was increased by about 5 times that of the prototype camera by improving the sensitivity and resolution of the depthmapping camera. Short video clips demonstrate how depth information from the camera can be used to create a virtual image in actual television program production. PMID- 19475122 TI - Modelling of microstructured waveguides using a finite-element-based vectorial mode solver with transparent boundary conditions. AB - A finite-element-based vectorial optical mode solver is used to analyze microstructured optical waveguides. By employing 1st-order Bayliss-Gunzburger Turkel-like transparent boundary conditions, both the real and imaginary part of the modal indices can be calculated in a relatively small computational domain. Results for waveguides with either circular or non-circular microstructured holes, solid- or air-core will be presented, including the silica-air Bragg fiber recently demonstrated by Vienne et al. (Post-deadline Paper PDP25, OFC 2004). The results of solid-core structures are in good agreement with the results of other methods while the results of air-core structure agree to the experimental results. PMID- 19475123 TI - Systematic analysis of wavelength conversion in a fiber optical parametric device with a single, tunable pump. AB - We present an experimental study of a systematic design procedure for achieving high bandwidth wavelength conversion with low ripple in a fiber parametric device with a single tunable pump.We find good agreement with established theory. Fourth order dispersion and fluctuations in the zero-dispersion wavelength have little effect on final conversion bandwidth. Strategies for ripple reduction and pump filtering in a practical device are proposed. PMID- 19475127 TI - Editorial--a light diagnosis. PMID- 19475128 TI - Vibrational spectroscopy: a clinical tool for cancer diagnostics. AB - Vibrational spectroscopy techniques have demonstrated potential to provide non destructive, rapid, clinically relevant diagnostic information. Early detection is the most important factor in the prevention of cancer. Raman and infrared spectroscopy enable the biochemical signatures from biological tissues to be extracted and analysed. In conjunction with advanced chemometrics such measurements can contribute to the diagnostic assessment of biological material. This paper also illustrates the complementary advantage of using Raman and FTIR spectroscopy technologies together. Clinical requirements are increasingly met by technological developments which show promise to become a clinical reality. This review summarises recent advances in vibrational spectroscopy and their impact on the diagnosis of cancer. PMID- 19475129 TI - Raman and CARS microspectroscopy of cells and tissues. AB - Raman spectroscopy has been recognized to be a powerful tool to study cells and tissues because the method provides molecular information without external markers such as stains or radioactive labels. To overcome the disadvantage of low signal intensities from most biomolecules, enhancement effects are utilized. A non-linear variant of Raman spectroscopy called coherent anti-Stokes Raman spectroscopy (CARS) belongs to the most promising techniques because it combines signal enhancement due to the coherent nature of the process with further advantages such as directional emission, narrow spectral bandwidth and no disturbing interference with autofluorescence. This review describes briefly the principles of the methods and summarizes applications to cells and tissues that are expected to gain significance in the future such as the combination with imaging approaches, microscopy, optical traps and fiber-optic probes. PMID- 19475130 TI - Emerging concepts in deep Raman spectroscopy of biological tissue. AB - This article reviews emerging Raman techniques for deep, non-invasive characterisation of biological tissues. As generic analytical tools, the new methods pave the way for a host of new applications including non-invasive bone disease diagnosis, chemical characterisation of 'stone-like' materials in urology and cancer detection in a number of organs. PMID- 19475131 TI - Detection of breast micro-metastases in axillary lymph nodes by infrared micro spectral imaging. AB - We report the ability of infrared micro-spectral imaging, coupled with completely unsupervised methods of multivariate statistical analysis, to accurately reproduce the histological architecture of axillary lymph nodes and detect metastatic breast cancer cells. The acquisition of spectral data from tissue embedded in paraffin provided spectra free of dispersive artefacts that may be observed for infrared microscopic measurements using a 'reflection/absorption' methodology. As a consequence, superior tissue classification and identification of cellular abnormality unattainable for deparaffinised tissue was achieved. PMID- 19475132 TI - Analysis of breast cancer by small angle X-ray scattering (SAXS). AB - Small angle X-ray scattering (SAXS) images of normal breast tissue and benign and malignant breast tumour tissues, fixed in formalin, were measured at the momentum transfer range of 0.063 nm(-1) < or = q (= 4pisin(theta/2)/lambda) < or = 2.720 nm(-1). Four intrinsic parameters were extracted from the scattering profiles (1D SAXS image reduced) and, from the combination of these parameters, another three parameters were also created. All parameters, intrinsic and derived, were subject to discriminant analysis, and it was verified that parameters such as the area of diffuse scatter at the momentum transfer range 0.50 < or = q < or = 0.56 nm(-1), the ratio between areas of fifth-order axial and third-order lateral peaks and third-order axial spacing provide the most significant information for diagnosis (p < 0.001). Thus, in this work it was verified that by combining these three parameters it was possible to classify human breast tissues as normal, benign lesion or malignant lesion with a sensitivity of 83% and a specificity of 100%. PMID- 19475133 TI - Factors influencing the discrimination and classification of prostate cancer cell lines by FTIR microspectroscopy. AB - In this study we obtained Fourier transform infrared (FTIR) spectra of fixed prostate cell lines of differing types as well as the primary epithelial cells from benign prostatic hyperplasia (BPH). Results showed that by using multivariate chemometric analysis it was possible to discriminate and classify these cell lines, which gave rise to sensitivity and specificity values of >94% and >98%, respectively. Following on from these results the possible influences of different factors on the discrimination and classification of the prostate cell lines were examined. Firstly, the effect of using different growth media during cell culturing was investigated, with results indicating that this did not influence chemometric discrimination. Secondly, differences in the nucleus-to cytoplasm (N/C) ratio were examined, and it was concluded that this factor was not the main reason for the discrimination and classification of the prostate cancer (CaP) cell lines. In conclusion, given the fact that neither growth media nor N/C ratio could totally explain the classification it is likely that actual biochemical differences between the cell lines is the major contributing factor. PMID- 19475134 TI - Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain. AB - A total of 1,429 serum samples from 389 consecutive patients with acute chest pain were analyzed with the goal to aid the rapid diagnosis of acute myocardial infarction. To the best of our knowledge this is the largest and most comprehensive study on mid-infrared spectroscopy in cardiology. We were able to identify those signatures in the mid-infrared spectra of the samples, which were specific to either acute myocardial infarction or chest pain of other origin (angina pectoris, oesophagitis, etc). These characteristic spectral differences were used to distinguish between the cause of the donor's acute chest pain using robust linear discriminant analysis. A sensitivity of 88.5% and a specificity of 85.1% were achieved in a blind validation. The area under the receiver operating characteristics curve amounts to 0.921, which is comparable to the performance of routine cardiac laboratory markers within the same study population. The biochemical interpretation of the spectral signatures points towards an important role of carbohydrates and potentially glycation. Our studies indicate that the "Diagnostic Pattern Recognition (DPR)" method presented here has the potential to aid the diagnostic procedure as early as within the first 6 hours after the onset of chest pain. PMID- 19475135 TI - Imminent cardiac risk assessment via optical intravascular biochemical analysis. AB - Heart disease is by far the biggest killer in the United States, and type II diabetes, which affects 8% of the U.S. population, is on the rise. In many cases, the acute coronary syndrome and/or sudden cardiac death occurs without warning. Atherosclerosis has known behavioral, genetic and dietary risk factors. However, our laboratory studies with animal models and human post-mortem tissue using FT IR microspectroscopy reveal the chemical microstructure within arteries and in the arterial walls themselves. These include spectra obtained from the aortas of ApoE-/- knockout mice on sucrose and normal diets showing lipid deposition in the former case. Also pre-aneurysm chemical images of knockout mouse aorta walls, and spectra of plaque excised from a living human patient are shown for comparison. In keeping with the theme of the SPEC 2008 conference 'Spectroscopic Diagnosis of Disease...' this paper describes the background and potential value of a new catheter-based system to provide in vivo biochemical analysis of plaque in human coronary arteries. We report the following: (1) results of FT-IR microspectroscopy on animal models of vascular disease to illustrate the localized chemical distinctions between pathological and normal tissue, (2) current diagnostic techniques used for risk assessment of patients with potential unstable coronary syndromes, and (3) the advantages and limitations of each of these techniques illustrated with patent care histories, related in the first person, by the physician coauthors. Note that the physician comments clarify the contribution of each diagnostic technique to imminent cardiac risk assessment in a clinical setting, leading to the appreciation of what localized intravascular chemical analysis can contribute as an add-on diagnostic tool. The quality of medical imaging has improved dramatically since the turn of the century. Among clinical non-invasive diagnostic tools, laboratory tests of body fluids, EKG, and physical examination are still the first line of defense. However, with the fidelity of 64-slice CT imaging, this technique has recently become an option when the patient presents with symptoms of reduced arterial flow. Single photon emission computerized tomography (SPECT) treadmill exercise testing is a standard non-invasive test for decreased perfusion of heart muscle, but is time consuming and not suited for emergent evaluation. Once the invasive clinical option of catherization is chosen, this provides the opportunity for intravascular ultrasound (IVUS) imaging. As the probe is pulled through the artery, the diameter at different parts is measurable, and monochrome contrast in the constricted area reveals the presence of tissue with a different ultrasonic response. Also, via an optical catheter with a fiber-optic conductor, the possibly of spectroscopic analysis of arterial walls is now a reality. In this case, the optical transducer is coupled to a near-infrared spectrometer. Revealing the arterial chemical health means that plaque vulnerability and imminent risk could be assessed by the physician. The classical emergency use of catherization involves a contrast agent and dynamic X-ray imaging to locate the constriction, determine its severity, and possibly perform angioplasty, and stent placement. PMID- 19475136 TI - Micro ATR-FTIR spectroscopic imaging of atherosclerosis: an investigation of the contribution of inducible nitric oxide synthase to lesion composition in ApoE null mice. AB - Inducible nitric oxide synthase (iNOS) has previously been shown to contribute to atherosclerotic lesion formation and protein nitration. Micro attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopic imaging was applied ex vivo to analyse lesions in atherosclerotic (ApoE-/-) mice. Histologies of cardiovascular tissue of ApoE-/- mice that contain the gene for iNOS and ApoE /- mice without iNOS (ApoE-/-iNOS-/- mice) were examined. Spectroscopic imaging of the aortic root revealed that iNOS did not affect the composition of the tunica media; furthermore, irrespective of iNOS presence, lipid esters were found to form the atherosclerotic plaque. ApoE-/- mouse aortic root lesions exhibited a more bulky atheroma that extended into the medial layer; signals characteristic of triglycerides and free fatty acids were apparent here. In ApoE-/-iNOS-/- mouse specimens, lesions composed of free cholesterol were revealed. ATR-FTIR spectra of the intimal plaque from the two mouse strains showed higher lipid concentrations in ApoE-/- mice, indicating that iNOS contributes to lesion formation. The reduction of lesion prevalence in ApoE-/-iNOS-/- mice compared with ApoE-/- mice is consistent with previous data. Moreover, the analysis of the plaque region revealed a change in the spectral position of the amide I band, which may be indicative of protein nitration in the ApoE-/- mouse, correlating with a more ordered (beta-sheet) structure, while a less ordered structure was apparent for the ApoE-/-iNOS-/- mouse, in which protein nitration is attenuated. These results indicate that micro ATR-FTIR spectroscopic imaging with high spatial resolution is a valuable tool for investigating differences in the structure and chemical composition of atherosclerotic lesions of ApoE-/- and ApoE /-iNOS-/- mice fed a high-fat Western diet and can therefore be applied successfully to the study of mouse models of atherosclerosis. PMID- 19475137 TI - Resonance Raman microscopy in combination with partial dark-field microscopy lights up a new path in malaria diagnostics. AB - Our goal is to produce a rapid and accurate diagnostic tool for malaria using resonance Raman spectroscopy to detect small inclusions of haemozoin in Plasmodium falciparum infected red blood cells. In pursuit of this aim we serendipitously discovered a partial dark-field effect generated by our experimental setup, which helps identify in thick blood films potential parasites that are normally difficult to see with conventional bright-field microscopy. The haemozoin deposits 'light up' and these can be selectively targeted with the Raman microscope to confirm the presence or absence of haemozoin by the strong 1569 cm(-1) band, which is a marker for haemozoin. With newly developed imaging Raman microscopes incorporating ultra-sensitive rapid readout CCDs it is possible to obtain spectra with a good signal-to-noise ratio in 1 second. Moreover, images from a smear of potentially infected cells can be recorded and analysed with multivariate methods. The reconstructed images show what appear to be sub-micron inclusions of haemozoin in some cells indicating that the technique has potential to identify low pigmented forms of the parasite including early trophozoite-stage infected cells. Further work is required to unambiguously confirm the presence of such forms through systematic staining but the results are indeed promising and may lead to the development of a new Raman-based malaria diagnostic. PMID- 19475138 TI - Morphology-sensitive Raman modes of the malaria pigment hemozoin. AB - Resonance Raman spectroscopy was applied for investigating the malaria pigment hemozoin, which is an important target structure of antimalarial drugs. Morphology-sensitive low wavenumber modes of hemozoin were selectively enhanced with help of excitation wavelengths at lambda = 633 nm and lambda = 647 nm. The assignment of the most prominent bands in the Raman spectra at 343 cm(-1) and 368 cm(-1) was assisted by DFT calculations of the hemozoin dimer. The mode at 343 cm(-1) in the Raman spectrum of hemozoin is strongly enhanced with lambda(exc.) = 647 nm and is represented by a combined, symmetric doming mode of the two hematin units in the hemozoin dimer. The enhancement of this vibration is stronger in the resonance Raman spectrum of hemozoin compared with less crystalline beta-hematin. The selective resonance enhancement of the morphology-sensitive Raman modes of hemozoin is caused by absorption bands in the UV-VIS-NIR spectrum. This absorption spectrum of the crystalline malaria pigment hemozoin shows a strong band at 655 nm. Another broad absorption band at 870 nm is the reason for the strong relative resonance enhancement of the mode at 1372 cm(-1) in the Raman spectrum of crystalline hemozoin with lambda(exc.) = 830 nm. In conclusion, resonance Raman micro-spectroscopy with lambda(exc.) = 647 nm was shown to have great potential as an analytical tool to probe the morphology of hematin samples. PMID- 19475139 TI - A candidate serum biomarker for bladder pain syndrome/interstitial cystitis. AB - Reliable diagnostic markers for Bladder Pain Syndrome/Interstitial Cystitis (IC) currently are not available. This study evaluated the feasibility of diagnosing IC in humans and domestic cats from the spectra of dried serum films (DSFs) using infrared microspectroscopy. Spectra were obtained from films from 29 humans and 34 domestic cats to create classification models using Soft Independent Modeling by Class Analogy (SIMCA). Ultrafiltration of serum improved discrimination capability. The classification models for both species successfully classified spectra based on condition (healthy/sick), and a different set of masked spectra correctly predicted the condition of 100% of the subjects. Classification required information from the 1500-1800 cm(-1) spectral region to discriminate between subjects with IC, other disorders, and healthy subjects. Analysis of cat samples using liquid chromatography-mass spectroscopy revealed differences in the concentration of tryptophan and its metabolites between healthy and affected cats. These results demonstrate the potential utility of infrared microspectroscopy to diagnose IC in both humans and cats. PMID- 19475140 TI - Rapid identification of Burkholderia cepacia complex species including strains of the novel Taxon K, recovered from cystic fibrosis patients by intact cell MALDI ToF mass spectrometry. AB - Two approaches based on intact cell matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (IC-MALDI-ToF MS) have been evaluated in order to discriminate and identify nine former Burkholderia cepacia complex (Bcc) species, Burkholderia contaminans belonging to the novel Taxon K, Burkholderia gladioli, and the most relevant non-fermentative (NF) Gram-negative rods recovered from cystic fibrosis (CF) sputum cultures. In total, 146 clinical isolates and 26 reference strains were analysed. IC mass spectra were obtained with high reproducibility applying a recently developed inactivation protocol which is based on the extraction of microbial proteins by trifluoroacetic acid (TFA). In a first approach, spectral analysis was carried out by means of a gel view representation of mass spectra, which turned out to be useful to recognize specific identifying biomarker proteins (SIBPs). A series of prominent mass peaks, mainly assigned to constitutively expressed proteins, were selected as SIBPs for identifications at the genus and species level. Two distinctive mass peaks present in B. contaminans spectra (7501 and 7900 Da) were proposed as SIBPs for the identification of this novel species. A second approach of spectral analysis based on data reduction, feature selection and subsequent hierarchical cluster analysis was used to obtain an objective discrimination of all species analysed. Both complementary modalities of analyzing complex IC-MALDI-ToF MS data open the path towards a rapid, accurate and objective means of routine clinical microbiology diagnosis of pathogens from sputum samples of CF patients. PMID- 19475141 TI - Phenotypic heterogeneity within microbial populations at the single-cell level investigated by confocal Raman microspectroscopy. AB - Single cells in genetically homogeneous microbial cultures exhibit marked phenotypic heterogeneity that is considered to bolster the fitness of the whole population. Heterogeneity on the single-cell level is typically masked in conventional studies of microbial populations, which rely on data averaged across thousands or millions of cells in a sample. Here we introduce confocal Raman microspectroscopy as a method for investigating and illustrating the spatial heterogeneity of microbial cell populations. By the use of three different test organisms as model systems, we show pronounced cellular heterogeneity even in colonies cultivated under laboratory conditions. PMID- 19475142 TI - Impact of fixation on in vitro cell culture lines monitored with Raman spectroscopy. AB - Raman spectroscopy provides chemical-rich information about the composition of analytes and is a powerful tool for biological studies. With the ability to investigate specific cellular components or image whole cells, compatible methods of sample preservation must be implemented for accurate spectra to be collected. Unfortunately, the effects of many commonly used sample preservation methods have not been explored with cultured cells. In this study, two human cell lineages of varying phenotypes were used to investigate the effects of sample preservation methods. Cells were cultured directly onto quartz substrates and either formalin fixed, desiccated or air dried. The results indicate that the methodology applied to cell cultures for Raman analysis significantly influences the quality and reproducibility of the resulting spectral data. Formalin fixation was not found to be as universally efficient as anticipated for a commonly used fixative. This was due largely to the inconsistency in sample preservation between cell lines and loss of signal intensity. Sample air-drying was found to be largely inconsistent in terms of spectral reproducibility. Our study shows that sample desiccation displayed good spectral reproducibility and resulted in a good signal to-noise ratio. Lipid and protein content in both activated and inactivated cells were maintained and provided a more controlled method compared with air-drying, revealing that the speed of drying is important for sample preservation. PMID- 19475143 TI - Correction of axial chromatic aberrations in confocal Raman microspectroscopic measurements of a single microbial spore. AB - Herein we describe a strategy for correcting the longitudinal or axial component of chromatic aberration in confocal Raman microspectroscopy. The method is based on measuring a vertical series of confocal Raman sections of samples by a high numerical aperture Raman microscope. Using the known characteristics of the wavelength-dependent focal shift of the optical system, the Raman intensities can be corrected to allow the rearrangement of Raman data from different focal planes. In the present study the computational correction routine was applied to an experimental data set of 4-dimensional (xyz spatial and the spectral dimension) confocal Raman spectra collected from single spores of Bacillus cereus. After correcting the axial component of the chromatic aberration, univariate and multivariate spectral parameters were obtained and used in the following for 3D segmentation and volume rendering on the basis of the structural and compositional information contained in the Raman spectra of the spore. Using univariate Raman intensities from defined functional group frequencies or k-means cluster membership values as a multivariate parameter for volume rendering, we demonstrate a high degree of correlation between confocal Raman microspectroscopy and the spores' morphology. In this paper we will also present cluster mean spectra which will be discussed in light of the presence of proteins and Ca-DPA, a calcium chelate of dipicolinic acid in the spore. PMID- 19475144 TI - Reflection contributions to the dispersion artefact in FTIR spectra of single biological cells. AB - Fourier transform infrared spectra of a single cell in transflection geometry are seen to vary significantly with position on the cell, showing a distorted derivative-like lineshape in the region of the optically dense nucleus. A similar behaviour is observable in a model system of the protein albumin doped in a potassium bromide disk. It is demonstrated that the spectrum at any point is a weighted sum of the sample reflection and transmission and that the dominance of the reflection spectrum in optically dense regions can account for some of the spectral distortions previously attributed to dispersion artefacts. Rather than being an artefact, the reflection contribution is ever present in transflection spectra and it is further demonstrated that the reflection characteristics can be used for cellular mapping. PMID- 19475145 TI - Spectroscopic signatures of single, isolated cancer cell nuclei using synchrotron infrared microscopy. AB - Single-cell studies have important implications in biomedicine. An accurate investigation of biochemical behaviour and status requires a biomolecular probe such as vibrational microscopy. Amongst other approaches, synchrotron infrared microspectroscopy is an appropriate analytical tool for single-cell investigation. However, it is important to understand the precise origin of spectral differences as they are directly related to the cell biochemistry. Beside biomolecular changes, physical properties can interfere in the resulting information, and the two effects need separating. Both cells and nuclei induce Mie scattering effects due to their equivalent size with the probe wavelength. This results in a large modification of the spectra, and its precise contribution has to be determined in order to extract the true spectral information. On this basis, we carried out this study in order to evaluate the exact contribution of cell nuclei to Mie scattering. To this purpose, we isolated whole cancer cell nuclei and obtained, for the first time, their FTIR spectra with good signal to noise ratio. The synchrotron-based FTIR (S-FTIR) spectra of nuclei showed changes in lipids, proteins, and DNA absorptions when compared to spectra of whole lung cancer cells. Importantly, we estimated the Mie scattering properties of single cells and single nuclei spectra and were consequently able to separate optical and chemical properties of single cells and nuclei. This is the first study which sheds new light on the identification of the precise spectral biomarkers of a whole cell and those of the cell nucleus. PMID- 19475146 TI - Raman spectroscopy--a potential platform for the rapid measurement of carbon nanotube-induced cytotoxicity. AB - In this study the suitability of Raman spectroscopy for the determination of carbon nanotube mediated toxicity on human alveolar carcinoma epithelial cells (A549) is explored. The exposure of this cell line represents the primary pathway of exposure in humans, that of inhalation. Peak ratio analysis demonstrates a dose-dependent response which correlates to previous toxicological studies. Principal component analysis is employed to further classify cellular response as a function of dose and to examine differences between spectra as a function of exposed concentration. To further illustrate the potential of Raman spectroscopy in this field, Partial Least Squares (PLS) regression and genetic algorithm feature selection have been utilised to demonstrate that clonogenic endpoints, and therefore toxic response, can be potentially predicted from spectra of cells exposed to un-determined doses, removing the need for costly and time consuming biochemical assays. This preliminary study demonstrates the potential of Raman spectroscopy as a probe of cytotoxicity to nanoparticle exposure. PMID- 19475147 TI - Picosecond Raman spectroscopy with a fast intensified CCD camera for depth analysis of diffusely scattering media. AB - A spectroscopic depth profiling approach is demonstrated for layers of non transparent, diffusely scattering materials. The technique is based on the temporal discrimination between Raman photons emitted from the surface and Raman photons originating from a deeper layer. Excitation was carried out with a frequency-doubled, 3 ps Ti:sapphire laser system (398 nm; 76 MHz repetition rate). Time-resolved detection was carried out with an intensified CCD camera that can be gated with a 250 ps gate width. The performance of the system was assessed using 1 mm and 2 mm pathlength cuvettes with powdered PMMA and trans stilbene (TS) crystals, respectively, or solid white polymer blocks: Arnite (polyethylene terephthalate), Delrin (polyoxymethylene), polythene (polyethylene) and Teflon (polytetrafluoroethylene). These samples were pressed together in different configurations and Raman photons were collected in backscatter mode in order to study the time difference in such media corresponding with several mm of extra net photon migration distance. We also studied the lateral contrast between two different second layers. The results demonstrate that by means of a picosecond laser system and the time discrimination of a gated intensified CCD camera, molecular spectroscopic information can be obtained through a turbid surface layer. In the case of the PMMA/TS two-layer system, time-resolved detection with a 400 ps delay improved the relative intensity of the Raman bands of the second layer with a factor of 124 in comparison with the spectrum recorded with a 100 ps delay (which is more selective for the first layer) and with a factor of 14 in comparison with a non-gated setup. Possible applications will be discussed, as well as advantages/disadvantages over other Raman techniques for diffusely scattering media. PMID- 19475148 TI - Method for automated background subtraction from Raman spectra containing known contaminants. AB - The use of Raman spectroscopy for biomedical applications requires overcoming the obstacle of the broad background that is also generated by biological samples. This background, which is often largely attributed to fluorescence, is frequently orders of magnitude greater than the Raman signal and needs to be removed in order to use Raman spectra in sample analysis. Several methods have been proposed for removing fluorescent signal, both instrumental and computational. Of the computational methods, polynomial fitting has become increasingly popular. Typically, a polynomial of approximately fifth order is used in the fitting. This method alone is not always capable of fitting some more tightly featured spectra that may be present in data, potentially coming from a contaminant in the sample itself or from the experimental design. If this signal is present in varying amounts, the polynomial background removal method can leave the residual spectra with non-uniform artifacts that hinder classification results. If a reference spectrum can be obtained for this interfering signal, however, it can be incorporated into the polynomial fit and removed separately. An automated method for the removal of broad and/or moderately featured background signal is described. In addition to simulations, the method has been applied to spectra from biofilms of Streptococcus mutans. PMID- 19475149 TI - ProRaman: a program to classify Raman spectra. AB - The program ProRaman, developed for the Matlab platform, provides an interactive and flexible graphic interface to develop efficient algorithms to classify Raman spectra into two or three different classes. A set of preprocessing algorithms to decrease the variable dimensionality and to extract the main features which improve the correct classification ratio was implemented. The implemented classification algorithms were based on the Mahalanobis distance and neural network. To verify the functionality of the developed program, 72 spectra from human artery samples, 36 of which had been histopathologically diagnosed as non diseased and 36 as having an atherosclerotic lesion, were processed using a combination of different preprocessing and classification techniques. The best result was accomplished when the variables were selected from the Raman spectrum shift range from 1200 to 1700 cm(-1), then preprocessed using wavelets for compression and principal component analysis for feature extraction and, finally, classified by a multilayer perceptron with one hidden layer with eight neurons. PMID- 19475150 TI - Differential diagnosis of cutaneous carcinomas by infrared spectral micro-imaging combined with pattern recognition. AB - Non-melanoma skin cancer includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease. The differential diagnosis of these lesions is sometimes difficult and relies on the histopathological examination of surgical specimens. However, a precise differential diagnosis is crucial for an accurate therapy and thus better patient care. FTIR spectral micro-imaging was applied directly on formalin-fixed paraffin-embedded samples of non-melanoma skin cancers. Chemometric and multivariate statistical analyses were developed to generate an automated IR-based histology without any chemical dewaxing. Different prediction models were developed using linear discriminant analysis combined with data reduction by Principal Component Analysis (PCA) or by wavenumber selection using statistical tests or genetic algorithms. Pseudo-colour maps were reconstructed and compared to conventional histology procedures. High correlation was obtained between the prediction maps and the histology which proves the great potential of FTIR spectroscopy for the differential diagnosis of skin carcinomas. PMID- 19475151 TI - A novel procedure for strain classification of fungal mycelium by cluster and artificial neural network analysis of Fourier transform infrared (FTIR) spectra. AB - Fourier transform infrared spectroscopy (FTIR) was used to discriminate important wood-destroying fungi. Mycelia of 26 fungal strains belonging to 24 different species were grown on agar plates and subjected to FTIR attenuated total reflection (ATR) measurements. To classify the FTIR spectra, cluster analysis--an unsupervised multivariate data analysis method--was compared with artificial neural network (ANN) analysis--a supervised approach. By internal validation, both methods classified 99% of the spectra correctly. External validation with independent test set spectra resulted in 95% correctly classified spectra, demonstrating the high potential of this method for fungal strain identification. PMID- 19475153 TI - Spectroscopic diagnosis of laryngeal carcinoma using near-infrared Raman spectroscopy and random recursive partitioning ensemble techniques. AB - In this work, we evaluated the diagnostic ability of near-infrared (NIR) Raman spectroscopy associated with the ensemble recursive partitioning algorithm based on random forests for identifying cancer from normal tissue in the larynx. A rapid-acquisition NIR Raman system was utilized for tissue Raman measurements at 785 nm excitation, and 50 human laryngeal tissue specimens (20 normal; 30 malignant tumors) were used for NIR Raman studies. The random forests method was introduced to develop effective diagnostic algorithms for classification of Raman spectra of different laryngeal tissues. High-quality Raman spectra in the range of 800-1800 cm(-1) can be acquired from laryngeal tissue within 5 seconds. Raman spectra differed significantly between normal and malignant laryngeal tissues. Classification results obtained from the random forests algorithm on tissue Raman spectra yielded a diagnostic sensitivity of 88.0% and specificity of 91.4% for laryngeal malignancy identification. The random forests technique also provided variables importance that facilitates correlation of significant Raman spectral features with cancer transformation. This study shows that NIR Raman spectroscopy in conjunction with random forests algorithm has a great potential for the rapid diagnosis and detection of malignant tumors in the larynx. PMID- 19475152 TI - Toward point-of-care diagnostic metabolic fingerprinting: quantification of plasma creatinine by infrared spectroscopy of microfluidic-preprocessed samples. AB - Infrared (IR) spectroscopy has previously been established as a means to accurately quantify several serum and urine metabolites, based upon spectroscopy of dry films. The same technique has also provided the basis to develop certain diagnostic tests, developed in the 'metabolomics' spirit. Here, we report on the further development of an integrated microfluidic-IR technology and technique, customized with the aim of dramatically extending the capabilities of IR spectroscopy in both analytical and diagnostic (metabolomic) applications. By exploiting the laminar fluid diffusion interface (LFDI), serum specimens are processed to yield product streams that are better suited for metabolic fingerprinting; metabolites are captured within the aqueous product stream, while proteins (which otherwise dominate the spectra of films dried from serum) are present in much reduced concentration. Spectroscopy of films dried from the aqueous stream then provides enhanced diagnostic and analytical sensitivity. The manuscript introduces an LFDI card design that is customized for integration with IR spectroscopy, and details the development of a quantitative assay for serum creatinine--based upon LFDI-processed serum samples--that is substantially more accurate (standard error of calibration, SEC = 43 micromol/L) than the corresponding assay based upon unprocessed serum specimens (SEC = 138 micromol/L). Preliminary results of diffusion modeling are reported, and the prospects for further optimization of the technique, guided by accurate modeling, are discussed. PMID- 19475154 TI - Characterization of Barrett esophagus and esophageal adenocarcinoma by Fourier transform infrared microscopy. AB - The objective of this exploratory study was to evaluate the feasibility of using Fourier-Transform Infrared (FTIR) spectromicroscopy to characterize formalin fixed, paraffin-embedded human esophageal tissues. Matched histologically normal esophageal squamous epithelium (NS), premalignant Barrett esophagus (BE), and primary esophageal adenocarcinoma (EADC) tissues, each defined according to strict clinicopathologic criteria, were obtained from patients who underwent esophageal resection. Using confocal IR microscopy, measurements in the mid-IR spectral region were carried out in transflection configuration, scanning regions of interest in 15 microm steps. A multidimensional dataset reporting the spectroscopic properties at each sampled point were analyzed by performing a hierarchical cluster analysis on the second derivative of spectral traces. Normal esophageal epithelia were characterized by a few well defined regions, mostly of large size (tens of contiguous pixels), which correlated with tissue histology, specifically the basal cell layer. BE tissues had characteristic regions localized to gland crypts, ranging in size from one pixel to a few tens of pixels, which displayed IR spectra with defined absorption features characteristic of glycoproteins. The incorporation of synchrotron light to improve the resolution of individual cells in BE tissues has demonstrated that these glycoproteins are associated with goblet cells, the characteristic cell type defining BE. Whereas the highly fragmented regions identified in EADC likely reflect tumor heterogeneity, FTIR mapping would appear to be a potentially useful technique to identify premalignant BE tissues. The technical feasibility of using FTIR to characterize formalin-fixed, paraffin-embedded human esophageal tissues demonstrates the potential of this technique to study archival human BE tissue specimens via automated screening techniques. PMID- 19475160 TI - Time-dependent density-functional theory. PMID- 19475161 TI - Time-dependent density functional theory of high excitations: to infinity, and beyond. AB - We review the theoretical background for obtaining both quantum defects and scattering phase shifts from time-dependent density functional theory. The quantum defect on the negative energy side of the spectrum and the phase shift on the positive energy side merge continuously at E=0, allowing both to be found by the same method. We illustrate with simple, one-dimensional examples: the spherical well and the delta well potential. As an example of a real system, we study in detail elastic electron scattering from the He+ ion. We show how the results are influenced by different approximations to the unknown components in (time-dependent) density functional theory: the ground state exchange-correlation potential and time-dependent kernel. We also revisit our previously obtained results for e-H scattering. Our results are remarkably accurate in many cases, but fail qualitatively in others. PMID- 19475162 TI - Time-dependent density functional theory versus Bethe-Salpeter equation: an all electron study. AB - We perform first-principle calculations for the macroscopic dielectric function within an all-electron full-potential framework, i.e., the linearized augmented planewave (LAPW) method. To this extent we pursue two different routes, which are, on the one hand, many-body perturbation theory (MBPT) by solving the Bethe Salpeter equation (BSE), and time-dependent density functional theory (TDDFT), on the other hand. The implementation into one program package, i.e., the EXC!TiNG code, allows a direct comparison of these approaches, in terms of accuracy as well as efficiency. We briefly review the theory, and describe in detail the quantities specific to the LAPW method. As an example we show the results for GaAs which is well-investigated in the literature, and hence serves as a stringent test case. PMID- 19475163 TI - TD-DFT calculations of electronic spectra of hydrogenated protonated polycyclic aromatic hydrocarbon (PAH) molecules: implications for the origin of the diffuse interstellar bands? AB - We report the application of time-dependent density functional theory (TD-DFT) to the calculation of electronic spectra of hydrogenated protonated polycyclic aromatic hydrocarbon (PAH) molecules. The hydrogen atoms lie on the periphery of the PAH structure and those considered here may be written Hn-HPAH+, where n is even. It is found, in common with protonated PAH molecules, HPAH+, that some of the electronic transitions fall in the visible spectral region. The implications of the results are discussed in the context of the long-standing enigmatic astronomical problem of the diffuse interstellar absorption bands. PMID- 19475164 TI - TDDFT diagnostic testing and functional assessment for triazene chromophores. AB - A simple diagnostic test based on orbital overlap [M. J. G. Peach et al., J. Chem. Phys., 2008, 128, 044118] may be used to help judge the reliability of excitation energies in time-dependent density functional theory (TDDFT) when using generalized gradient approximation (GGA) and hybrid functionals. Orbital plots are used to illustrate the test for a model tripeptide and for 4-(N,N dimethylamino)benzonitrile, which are representative of systems containing low- and high-overlap charge-transfer excitations. The scheme is then applied to a series of triazene chromophores in solvent, highlighting the relationship between overlap and oscillator strength and its implications for theoretical absorption spectra. No low-overlap excitations are observed with a hybrid functional; a single one is identified using a GGA. To assess the diagnostic test and to judge functional performance, gas phase triazene TDDFT excitations are compared with correlated ab initio values. The diagnostic test correctly identifies two low overlap problematic GGA excitations. However, it does not identify another problematic excitation where the electron is excited to a spatially extended orbital, which necessarily has reasonable overlap with the occupied orbital; an improved diagnostic quantity is required for such cases. The best agreement between TDDFT and correlated ab initio excitations is obtained using a Coulomb attenuated functional; the errors are significantly smaller than from the GGA and hybrid functionals. The study provides further support for the high quality excitations from Coulomb-attenuated functionals, negating the need for diagnostic tests. PMID- 19475165 TI - An ab initio and TD-DFT study of solvent effect contributions to the electronic spectrum of Nile Red. AB - A CIS and TD-DFT study using a polarizable continuum solvent model has been conducted to assess non-specific solvent effects on the spectral shifts in Nile Red (NR). The results in this paper show that the electronic band shifts of Nile Red are a consequence of both a field effect on the transition energy and an effect due to a solvent induced geometry change. The S0-->S1 transition experiences a large red-shift with increasing solvent polarity but is relatively insensitive to geometric change. The TD-B3LYP assessment of the S0-->S2 transition yields a blue shift with increasing solvent polarity but a red shift due to the solvent induced geometry change. Ground state dipole moments and polarizabilities are also shown to increase with solvent polarity. CIS optimization of the first excited state of NR is reported, but the solvent effects suggest a locally excited state may have been obtained. Further studies are needed to assess the role of a TICT state. PMID- 19475166 TI - Towards a gauge invariant method for molecular chiroptical properties in TDDFT. AB - We present an efficient scheme to calculate the chiroptical response of molecular systems within time dependent density functional theory using either a real-time propagation or a frequency-dependent Sternheimer method. The scheme avoids the commonly used sum over empty orbitals and has a very favorable scaling with system size. Moreover, the method is general and can be easily implemented. In the present work, we implemented it using a real-space pseudo-potential representation of the wave-functions and Hamiltonian. The specific use of non local pseudo-potentials implies that a gauge correction term in the angular momentum operator must be included to ensure that the total scheme is fully gauge invariant. Applications to small organic chiral molecules are shown and discussed, addressing some deficiencies of present exchange-correlation functionals to describe the absolute position of the excitations. However, the shape or sign of the dichroism spectra comes out in excellent agreement with available experiments. PMID- 19475167 TI - Second-order nonlinear optical properties of transition metal clusters [MoS4Cu4X2Py2] (M=Mo, W; X=Br, I). AB - We present in this paper the second-order nonlinear optical properties of a series of penta-nuclear metal clusters [MS4Cu4X2Py6] (M=Mo, W; X=Br, I) on the basis of the hyper-Rayleigh scattering experiments and the first-principle calculations (TDDFT). The measurements obtain the notably large dynamic quadratic hyperpolarizabilities at 1064 nm [beta(-2omega, omega, omega) values are around 200x10(-30) esu] and, by extrapolation, a large static values around 60x10(-30) esu. The computational results of the electronic excitation energies and quadratic hyperpolarizabilities by TDDFT method are in good agreement with the experimental values and by careful examination they are both dependent on the nature of the metals. The in-depth analysis of the mechanism for the second-order response unambiguously shows the evidence of the contribution of direct metal metal interaction charge transfers. This provides a new tool to tune nonlinear optical properties in exploiting metal cluster materials and molecular devices. PMID- 19475168 TI - Absorption and fluorescence properties of oligothiophene biomarkers from long range-corrected time-dependent density functional theory. AB - The absorption and fluorescence properties in a class of oligothiophene push-pull biomarkers are investigated with a long-range-corrected (LC) density functional method. Using linear-response time-dependent density functional theory (TDDFT), we calculate excitation energies, fluorescence energies, oscillator strengths, and excited-state dipole moments. To benchmark and assess the quality of the LC TDDFT formalism, an extensive comparison is made between LC-BLYP excitation energies and approximate coupled cluster singles and doubles (CC2) calculations. When using a properly-optimized value of the range parameter, mu, we find that the LC technique provides an accurate description of charge-transfer excitations as a function of biomarker size and chemical functionalization. In contrast, we find that re-optimizing the fraction of Hartree Fock exchange in conventional hybrid functionals still yields an inconsistent description of excitation energies and oscillator strengths for the two lowest excited states in our series of biomarkers. The results of the present study emphasize the importance of a distance-dependent contribution of exchange in TDDFT for investigating excited state properties. PMID- 19475169 TI - Time-dependent current-density functional theory for generalized open quantum systems. AB - In this article, we prove the one-to-one correspondence between vector potentials and particle and current densities in the context of master equations with arbitrary memory kernels, therefore extending time-dependent current-density functional theory (TD-CDFT) to the domain of generalized many-body open quantum systems (OQS). We also analyse the issue of A-representability for the Kohn-Sham (KS) scheme proposed by D'Agosta and Di Ventra for Markovian OQS [Phys. Rev. Lett. 2007, 98, 226403] and discuss its domain of validity. We suggest ways to expand their scheme, but also propose a novel KS scheme where the auxiliary system is both closed and non-interacting. This scheme is tested numerically with a model system, and several considerations for the future development of functionals are indicated. Our results formalize the possibility of practising TD CDFT in OQS, hence expanding the applicability of the theory to non-Hamiltonian evolutions. PMID- 19475170 TI - Optical and magnetic properties of boron fullerenes. AB - We report linear response properties of the recently proposed boron fullerenes [N. Gonzalez Szwacki et al., Phys. Rev. Lett., 2007, 98, 166804]: magnetic susceptibilities, static dipole polarizabilities and dynamical polarizabilities (i.e. optical and near ultraviolet absorption spectra), calculated from first principles within the (time-dependent) density-functional theory framework. We find that all clusters except B80 are diamagnetic. The strong cancellation between diamagnetic and paramagnetic currents in B80 leads to a very small value for its susceptibility that turns out to be slightly paramagnetic. Static polarizabilities increase linearly with the number of B atoms. Furthermore, the absorption spectrum of B80 is very different from the one of its carbon counterpart C60, exhibiting a low absorption threshold of about 1.5 eV and many peaks in the visible and near ultraviolet. This can be understood by the analysis of the wavefunctions involved in the low energy transitions. PMID- 19475171 TI - Inhomogeneous STLS theory and TDCDFT. AB - We consider the inhomogeneous Singwi-Tosi-Land-Sjolander theory (ISTLS) of Dobson, Wang and Gould (Phys. Rev. B, 2002, 66, 081108(R)), and possible generalizations, in the context of time dependent current density functional theory (TDCDFT) and its tensor exchange correlation kernel fxc. We show that ISTLS corresponds to an fxc that is nonlocal in space but has only a trivial frequency dependence, and only a very simple tensorial structure. We propose approaches that may obtain more realistic structure while retaining the positive ISTLS features, namely that strong spatial inhomogeneity is allowed, with a kernel that contains physics specific to the inhomogeneous system under study, rather than being based on uniform-gas data. PMID- 19475172 TI - Bound states in time-dependent quantum transport: oscillations and memory effects in current and density. AB - The presence of bound states in a nanoscale electronic system attached to two biased, macroscopic electrodes is shown to give rise to persistent, non-decaying, localized current oscillations which can be much larger than the steady part of the current. The amplitude of these current oscillations and of the corresponding density oscillations depends on the entire history of the applied potential. The bound-state contribution to the time-averaged density turns out to be history dependent as well and leads to a natural definition of the bound-state occupations out of equilibrium. PMID- 19475173 TI - Time-dependent density functional theory for resonant properties: resonance enhanced Raman scattering from the complex electric-dipole polarizability. AB - Based on resonant-convergent-and thereby complex-electric-dipole polarizabilities, formulae for differential cross sections in resonant Raman spectroscopy are presented. In absorptive regions of the spectrum, there are phase delays in the induced polarization that enter the expressions for the cross sections. The theory is exemplified by calculations employing the adiabatic time dependent density functional theory approximation, with applications on the low lying, dipole-allowed, electronic states of a sample of molecules, including hydrogen peroxide, pyridine, and trinitrotoluene. Results obtained with the Coulomb attenuated B3LYP exchange-correlation functional are found to be more accurate than those obtained with the conventional B3LYP functional-an observation that holds not only for trinitrotoluene with its transitions of charge-transfer character but also for the other cases. The qualitative features of the resonant Raman spectra for a given molecule vary strongly from one resonance wavelength to another, which is a fact that could further facilitate the use of this spectroscopy in applications of stand-off detection of gaseous samples in ultra-low concentrations. PMID- 19475174 TI - On the proton transfer mechanism in ammonia-bridged 7-hydroxyquinoline: a TDDFT molecular dynamics study. AB - We have investigated the mechanism of proton transfer in the lowest photoexcited state of 7-hydroxyquinoline.(NH3)3 using TDDFT based molecular dynamics. We observe a concerted mechanism according to which all protons are transferred simultaneously in a fast process (approximately 100 fs) that amounts to the net transport of one proton from the oxygen to the nitrogen of 7-hydroxyquinoline. In addition, the observed proton transfer pathway involves all three ammonia molecules and not only two as previously proposed. These differences arise from dynamical effects that occur at finite temperature. Our simulations provide a detailed time-resolved description of the proton transfer reaction mechanism for a prototypical molecular cluster and thus help to shed further light on the nature of this important and ubiquitous process. PMID- 19475175 TI - Chemical and protein shifts in the spectrum of the photoactive yellow protein: a time-dependent density functional theory/molecular mechanics study. AB - We have studied the light absorption properties of the p-coumaric acid chromophore in the photoactive yellow protein (PYP) with a hybrid time-dependent density functional theory/molecular mechanics (TDDFT/MM) method. To critically assess the performance of TDDFT for this specific system, we first evaluated in vacuo the excited states of several PYP chromophore models. We then calculated the absorption maximum of the phenolate anion of the thiomethyl-p-coumaric acid (TMpCA-) in the protein. Although within the limitations of TDDFT in describing charge-transfer and resonance excited states, we confirm a sizeable red shift in the absorption maximum due to the chemical differences between the free chromophore and that in the protein. The interaction between the chromophore and the protein environment induces a very small spectral shift, in line with experimental evidence. Comparison between the vertical electron detachment energy of the chromophore in vacuo and in the protein reveals that the protein stabilizes the choromophore in the excited states by preventing radical formation. PMID- 19475176 TI - Excitation energies from ground-state density-functionals by means of generator coordinates. AB - The generator-coordinate method is a flexible and powerful reformulation of the variational principle. Here we show that by introducing a generator coordinate in the Kohn-Sham equation of density-functional theory, excitation energies can be obtained from ground-state density functionals. As a viability test, the method is applied to ground-state energies and various types of excited-state energies of atoms and ions from the He and the Li isoelectronic series. Results are compared to a variety of alternative DFT-based approaches to excited states, in particular time-dependent density-functional theory with exact and approximate potentials. PMID- 19475177 TI - A time-dependent density-functional approach to nonadiabatic electron-nucleus dynamics: formulation and photochemical application. AB - To study nonadiabatic dynamics of the electrons and nuclei, the quantum chemical wavefunction methods have often been invoked to compute the nonadiabatic couplings (NACs), but time-dependent density functional theory (TD-DFT) can provide a formally exact alternative approach when the ground and one excited electronic states are concerned. Based on the density response scheme to compute the NAC vectors [J. Chem. Phys., 2007, 127, 064103], herein presented are a full quantum wave packet and a semi-classical surface hopping approach to the nonadiabatic chemical reactions for the electronically ground and excited states. The adiabatic local density approximation (ALDA) was used here but, contrary to previous simulations based on DFT or TD-DFT, no further approximations were made for the electrons. With those approaches we could successfully describe the photochemical syn-anti isomerization dynamics of a formaldimine molecule (CH2=NH) and investigate the dissipation effects with use of a Langevin dynamics scheme. These simulations demonstrated an important role played by the dissipation and suggested that accurately modeling the dissipation is the next step towards a truly ab initio prediction. PMID- 19475178 TI - Wavepacket basis for time-dependent processes and its application to relaxation in resonant electronic transport. AB - Stroboscopic wavepacket basis sets [P. Bokes, F. Corsetti, R. W. Godby, Phys. Rev. Lett., 2008, 101, 046402] are specifically tailored for a description of time-dependent processes in extended systems, such as non-periodic geometries of various contacts consisting of solids and molecules. The explanation of the construction of such a basis for two simple finite systems is followed by a review of the general theory for extended systems with continuous spectrum. The latter is further elaborated with the introduction of the interaction representation which takes full advantage of the time-dynamics built into the basis. The formalism is applied to a semi-analytical example of electronic transport through resonant tunnelling barrier in 1D. Through the time-dependent generalisation of the Landauer formula given in terms of the Fourier expansion of the transmission amplitude we analyze the temporal character of the onset of the steady-state. Various time-scales in this process are shown to be directly related to the energetic structure of the resonant barrier. PMID- 19475179 TI - Can phthalocyanines and their substituted alpha-para-(methoxy)phenyl derivatives act as photosensitizers in photodynamic therapy? A TD-DFT study. AB - A time-dependent density functional theory study (TD-DFT) is presented regarding the substituent effects on the Q-bands of two classes of non-planar phthalocyanines: the alpha-octaphenyl and p-alpha-octamethoxyphenyl substituted compounds, in their free-base and zinc complex forms. Singlet vertical excitation energies, computed at the PBE0/SVP//BP86/SVP level of theory also including bulk solvent effects (COSMO model), resulted within 0.1 eV of experiment. The experimental red-shift for the Q-band, going from the phenylated to the methoxyphenylated case, was well-reproduced theoretically and in the latter case it was found to depend mainly on the nature of the substituents and partly on structure distortion effects. The energetic gap between the singlet ground and first triplet excited state was calculated in solvent to be 1.28 eV for the free base phthalocyanine (H2Pc) and 1.45 eV for the unsubstituted zinc complex (ZnPc) and lower than 0.98 eV for all the other compounds, which is the energetic lower limit for a molecule to act as photosensitiser in photodynamic therapy according to a Type II reaction mechanism. As a consequence, since this property requirement for drugs used in photodynamic therapy is not fulfilled by the investigated near-infrared photosensitizers, they cannot be proposed as candidates for their use in this medical treatment. PMID- 19475180 TI - Substituent effects on the light-induced C-C and C-Br bond activation in (bisphosphine)(eta2-tolane)Pt0 complexes. A TD-DFT study. AB - A theoretical study of the steric and electronic effects of different substituents on the electronic ground and excited states of (bisphosphine)(eta2 tolane)Pt0 complexes is presented. A natural-bond-order (NBO) analysis has been performed to describe the bonding nature of the "hapto-like" coordination of the Pt atom to the alkyne bond of the tolane group. The results show an important contribution of the pi-back donation in all complexes, amounting to half of the energy associated to the sigma-bonding interaction. A TD-DFT study of the absorption spectra helps rationalizing the photochemistry of the complexes. Metal ligand charge transfer (MLCT) transitions from the Pt atom to the alkyne are assigned as the photochemical "active" states responsible for C-C bond cleavage. Electronic excitations to the sigma* orbital of the C-Br bond are involved in C Br bond activation. It is shown that both steric and electronic effects play an important role in determining the presence of these electronic excitations. PMID- 19475181 TI - Photodegradation mechanism of the common non-steroid anti-inflammatory drug diclofenac and its carbazole photoproduct. AB - Diclofenac (DF) is a widely used non-steroid anti-inflammatory drug, associated with a range of side effects. The phototoxicity of DF is studied herein employing computational quantum chemistry at the B3LYP/6-31G(d,p) level of theory. The results show that the drug readily absorbs radiation from the UV-region. The deprotonated form spontaneously dechlorinates from its triplet state leading to ring closure and formation of an active photoproduct: chlorocarbazole acetic acid, CCA. The formed CCA is also photodegraded easily from its deprotonated triplet state. Photodegradation routes of deprotonated CCA are decarboxylation (barrier less than 4.5 kcal mol(-1)) and dechlorination (barrier around 6.2 kcal mol(-1)). The energy barrier required for dechlorination to take place from the neutral from is about 20 kcal mol(-1). The differences between the molecular orbitals of the neutral and the deprotonated forms of DF and CCA and spectra obtained using time-dependent density-functional theory (TD-DFT), in addition to the different radical and oxygenated intermediate species formed during the photodegradation mechanism, are discussed in more detail. The theoretical results obtained herein are in line with the experimental results available to date. PMID- 19475183 TI - Time-dependent current density functional theory via time-dependent deformation functional theory: a constrained search formulation in the time domain. AB - The logical structure and basic theorems of time-dependent current density functional theory (TDCDFT) are analyzed and reconsidered from the point of view of recently proposed time-dependent deformation functional theory (TDDefFT). It is shown that the formalism of TDDefFT allows to avoid a traditional external potential-to-density/current mapping. Instead the theory is formulated in a form similar to the constrained search procedure in the ground state DFT. Within this formulation of TDCDFT all basic functionals appear from the solution of a constrained universal many-body problem in a comoving reference frame, which is equivalent to finding a conditional extremum of a certain universal action functional. As a result the physical origin of the universal functionals entering the theory, as well as their proper causal structure become obvious. In particular, this leaves no room for any doubt concerning the predictive power of the theory. PMID- 19475182 TI - Computation of accurate excitation energies for large organic molecules with double-hybrid density functionals. AB - Time-dependent double-hybrid density functional methods are evaluated for the calculation of vertical singlet-singlet valence excitation energies of a wide variety of organic molecules. Beside the already published TD-B2-PLYP method, an analogous approach based on the recently published ground state B2GP-PLYP functional is presented for the first time. Double-hybrid functionals contain a hybrid-GGA-like part for which a conventional TDDFT linear response treatment is carried out. The thus obtained excitation energies are afterwards corrected by adding a non-local correlation portion, which is based on an CIS(D) type excited state perturbative correction. Both, TD-B2-PLYP and TD-B2GP-PLYP, are first applied to the 142 vertical singlet excitation energies in a benchmark set by Schreiber et al., that contains small and medium sized organic molecules. In a second part, a new benchmark set composed of five large organic dyes is proposed. Accurate reference values are derived from experimental 0-0 excitation energies in solution. A back-correction scheme based on TDDFT computations is presented by which solvent, relaxation and vibrational effects are removed, yielding experimental vertical gas phase excitation energies with an estimated accuracy of about +/-0.1 eV. The TD-B2-PLYP, TD-B2GP-PLYP and a variety of conventional TDDFT methods are then applied to this new benchmark set. The results for both considered test sets show that the new double-hybrid approaches yield the smallest mean absolute deviations of 0.22 eV for the first benchmark set and 0.19 eV (TD-B2-PLYP) and 0.16 eV (TD-B2GP-PLYP) for the new organic dye test set. Apart from a break-down of the perturbative correction for very high-lying transitions (larger than 8 eV), it is generally found that the double-hybrid functionals show high robustness and accuracy that cannot be obtained with conventional density functionals (e.g. B3-LYP). PMID- 19475184 TI - Photoabsorption spectra from adiabatically exact time-dependent density functional theory in real time. AB - Photoabsorption spectra for 2-electron singlet systems are obtained from the real time propagation of the time-dependent Kohn-Sham equations in the adiabatically exact approximation. The latter is provided by the exact ground state exchange correlation potential corresponding to the instantaneous density. The results are compared to exact data obtained from the solution of the interacting Schrodinger equation. We find that the adiabatically exact approximation provides very good results for transitions of genuinely single excitation character but yields incorrect results if double excitations contribute substantially. However, the extent of the error can vary: some double excitations are just shifted in energy whereas others are missed completely. These situations are analyzed with the help of transition densities. PMID- 19475185 TI - Double excitation effect in non-adiabatic time-dependent density functional theory with an analytic construction of the exchange-correlation kernel in the common energy denominator approximation. AB - Time-dependent density functional (response) theory (TDDF(R)T) is applied almost exclusively in its adiabatic approximation (ATDDFT), which is restricted to predominantly single electronic excitations and neglects additional roots of the TDDFT eigenvalue problem stemming from the interaction between single and double excitations. We incorporate the effect of the latter interaction into a non adiabatic frequency-dependent and spatially non-local Hartree-exchange correlation (Hxc) kernel fCEDAHxc (r1, r2, omega), the explicit analytical expression of which is derived for interacting single and double excitations well separated from the other excitations, within the common energy denominator approximation (CEDA) for the Kohn-Sham (KS) and interacting density response functions, chis and chi, respectively. The kernel fCEDAHxc (r1, r2, omega) obtained from the direct analytical inverse of chiCEDAs and chiCEDA is a sum of the delta-function and non-local orbital-dependent spatial terms with frequency dependent factors, with which fCEDAHxc acquires a modulated quadratic dependence on omega. The effective incorporation in fCEDAHxc of the complete manifold of excited states (through the delta function term) represents an extension of the kernel reported by Maitra, Zhang, Cave, and Burke [J. Chem. Phys., 2004, 120, 5932]. In the TDDFT eigenvalue equations considered in the diagonal approximation, fCEDAHxc generates two excitation energies omegaq and omegaq+1, which both correspond to the same single KS excitation omegasq, thus producing the effect of the single-double excitation interaction. PMID- 19475186 TI - Physical signatures of discontinuities of the time-dependent exchange-correlation potential. AB - The exact exchange-correlation (XC) potential in time-dependent density functional theory (TDDFT) is known to develop steps and discontinuities upon change of the particle number in spatially confined regions or isolated subsystems. We demonstrate that the self-interaction corrected adiabatic local density approximation for the XC potential has this property, using the example of electron loss of a model quantum well system. We then study the influence of the XC potential discontinuity in a real-time simulation of a dissociation process of an asymmetric double quantum well system, and show that it dramatically affects the population of the resulting isolated single quantum wells. This indicates the importance of a proper account of the discontinuities in TDDFT descriptions of ionization, dissociation or charge transfer processes. PMID- 19475187 TI - Autoionizing resonances in time-dependent density functional theory. AB - Autoionizing resonances that arise from the interaction of a bound single excitation with the continuum can be accurately captured with the presently used approximations in time-dependent density functional theory (TDDFT), but those arising from a bound double excitation cannot. In the former case, we explain how an adiabatic kernel, which has no frequency-dependence, can yet generate the strongly frequency-dependent resonant structures in the interacting response function, not present in the Kohn-Sham response function. In the case of the bound double-excitation, we explain that a strongly frequency-dependent kernel is needed, and derive one as an a posteriori correction to the usual adiabatic approximations in TDDFT. Our approximation becomes exact for an isolated resonance in the limit of weak interaction, where one discrete state interacts with one continuum. We derive a "Fano TDDFT kernel" that reproduces the Fano lineshape within the TDDFT formalism, and also a dressed kernel, that operates on top of an adiabatic approximation. We illustrate our results on a simple model system. PMID- 19475188 TI - The polarizability in solution of tetra-phenyl-porphyrin derivatives in their excited electronic states: a PCM/TD-DFT study. AB - Time dependent density functional theory and polarizable continuum model have been used to describe tetra-phenyl-porphyrin derivatives in different solvents and at different pH values. Our results show that last generation functionals are able to describe with good accuracy the photophysics of the title compounds, including different physical-chemical properties of excited electronic states. In particular, the strong modification of polarizabilities induced in some cases by electron excitation could explain a recent hypothesis about NLO characteristics of specific porphyrin adducts. PMID- 19475189 TI - A new generalized Kohn-Sham method for fundamental band-gaps in solids. AB - We developed a method for calculating the ground-state properties and fundamental band-gaps of solids, using a generalized Kohn-Sham approach combining a local density approximation (LDA) functional with a long-range explicit exchange orbital functional. We found that when the range parameter is selected according to the formula gamma=A/(epsiloninfinity-epsilon) where epsiloninfinity is the optical dielectric constant of the solid and epsilon=0.84 and A=0.216 a0(-1), predictions of the fundamental band-gap close to the experimental values are obtained for a variety of solids of different types. For most solids the range parameter gamma is small (i.e. explicit exchange is needed only at long distances) so the predicted values for lattice constants and bulk moduli are similar to those based on conventional LDA calculations. Preliminary calculations on silicon give a general band structure in good agreement with experiment. PMID- 19475192 TI - [Mental Health in primary care]. PMID- 19475193 TI - [Mental Health Action Plan: contextual analysis and elements impacting on organization of primary care services and collaborative issues]. AB - Since 2005, the Mental Health Action Plan maps out development and reorganization of mental health services in Quebec. With concurrent reforms affecting the overall layout of the health care system, the Action Plan especially seeks to improve the management of common mental disorders. This particular concern calls for transformations at the primary care level. Contextual analysis of contrasting settings allows the identification of the main determinants in this actual process of change and in the ways collaborative issues are addressed. PMID- 19475194 TI - [General practitioners: practices and integration of mental health care in Quebec]. AB - This article examines the socio-demographic profile of general practitioners (GPs), their role in the management of (transient/moderate, severe/chronic) mental health disorders in different areas (urban, semi-urban, and rural) of Quebec as well as if their clinical practice and collaboration are oriented towards integration of mental health services. This crosswise study is based on 398 GPs representative of all Quebec GPs who answered a questionnaire. The study shows that GPs play a central role in mental health. According to territories, they have different socio-demographic and practice profiles. The types of territory and the degree of severity of mental health illnesses influence the propensity of GPs to integrate mental health care. Finally, GPs practiced mostly in silo, but they support greater integration of mental health services. The authors conclude that to improve mental health services integration, more proactive incentives should be favoured by political elites, adapted to the severity of the case and environments (urban, semi-urban or rural). However, the shortage of resources that is particularly striking in rural areas as well as inadequate mechanisms for clinical decision, reduce inter-relations and seriously limit the integration of healthcare. PMID- 19475196 TI - [Mental health community organizations in Quebec: role and partnership models]. AB - This study presents a global picture of the 371 government funded community-based mental health organizations (OCSM) and provides a description of the partnerships developed with community, institutional and inter-sector networks. The authors examine the diversity of the mental health community organizations based on the following characteristics: date of foundation, type and extent of territory, type and number of services offered, financial statement; participation in associations, participation in steering committees and models of partnership. The surface area of the territory, the size of the budget as well as involvement in steering committees appear to be enabling factors favouring the development of relations between organizations. PMID- 19475195 TI - [Major depression in primary care and clinical impacts of treatment strategies: a literature review]. AB - Major or clinical depression represents a frequent mental illness that is often associated with a high level of morbidity and mortality. Yet, major depression remains under-diagnosed and under-treated. On the level of treatment, it would appear desirable for reasons of better prognosis, to aim more than the simple reduction of depressive symptoms and target their remission resolutely and the fastest return to the individual's optimal functioning. This article presents a systematic review of the literature relating to the clinical impacts of treatment strategies aiming at the improvement of services offered to people who suffer of clinical depression and who consult in primary care. The authors summarize results drawn from 41 studies that include a measurement of the clinical impacts (reduction of symptoms, response, remission and functioning) of various treatment strategies. It appears that using complex treatment strategies favour positive outcomes. The authors propose various paths of research to further increase current knowledge. PMID- 19475197 TI - [Preliminary qualitative evaluation of a shared-care mental health programme with youths in Montreal: facing institutional and cultural uncertainty]. AB - This article describes a collaborative mental health care project for youths, implemented in Montreal in a multiethnic setting. The authors examine the adjustments needed in the shared-care model to address the complexity of cultural and cooperation issues raised in the provision of services to a multiethnic population. A preliminary qualitative evaluation of the project shows how first line workers face many uncertainties, stemming from both the institutional context and the multicultural reality of the population served. Results from this study advance the hypothesis that although uncertainties may generate discomfort and confusion, they may also open a space for innovation and acceptance of otherness. PMID- 19475198 TI - [Cross training program in Montreal's south west: best practices and training in a context of continuum of services in mental health care and addiction treatment]. AB - This article presents the cross training program in Montreal's south-west. The authors underline that the context of post-deinstitutionalization and mental health service integration impose new roles to professionals who work within these different networks of services. Cross training thus appears as a model that is particularly adapted to their needs in order to optimize their interventions. The model is presented with a review of the most recent studies and is illustrated with the cross training program, a model developed by the networks of mental health care and addiction treatment in Montreal's south-west. The program's applications are examined for other networks of care and services. PMID- 19475199 TI - [Can mental health problems be diagnosed by general physicians? Perspectives of family physicians according to administrative standards]. PMID- 19475200 TI - [Role of family physicians in the treatment of psychoses]. PMID- 19475201 TI - [Agreement between the Federation of family physicians of Quebec and the minister of Health and Social Services: impact on mental health]. PMID- 19475202 TI - [Panic disorders combined with agoraphobia and social anxiety disorder: need for health aids and access to treatment]. PMID- 19475203 TI - [Usefulness of psychological education in the integrated treatment of personality disorders]. PMID- 19475204 TI - [Experience with the tools of mental health as the first line of importance in the improvement of health care]. PMID- 19475206 TI - [Can one import an integrated model of health services for the aged in the context of autonomy in mental health?]. PMID- 19475205 TI - [Toward integrated care in mental health: experience in the area of Prepsy]. PMID- 19475207 TI - [The impact of autism on the life of parents]. AB - The aim of this paper is to explore the stress and the psychological distress faced by parents of children living with different types of disability. Its main focus is on parents of children with autism. The first part describes the stress factors faced by parents of children with disabilities and the second, the particularities of the stress faced by parents of children with autism. The third part explores other types of stress factors, such as financial problems, marital discord or beak-up, single parenthood and lack of social support. In the forth part, we examine weather the services are well suited to provide for the needs of families, and, in the fifth part, we describe the major role played by intervention in the life of families of children with autism. PMID- 19475208 TI - Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by bispectral index, suppression rate and electroencephalographic power spectral analysis. AB - BACKGROUND AND OBJECTIVES: Dexmedetomidine, an alpha2-adrenergic agonist, has been described as being able to decrease the demand for both venous and inhalational agents. This study aimed at evaluating the influence of Dexmedetomidine upon sevoflurane end-expiratory concentration (EC) with monitoring the depth of anesthesia. METHODS: Participated in this study 40 female adult patients, physical status ASA I, submitted to gynecological laparoscopy under general anesthesia maintained with sevoflurane, who were randomly divided in two groups: Group I (n=20), without dexmedetomidine; and Group II (n=20), with dexmedetomidine, in continuous infusion, as follows: Rapid phase (1 microg kg(-1) in 10 min(-1)) 10 minutes before anesthesia induction, followed by a maintenance phase (0.4 microg kg(-1) h(-1)) throughout the surgery. The following parameters were analyzed: BP, HR, BIS, SEF 95%, delta%, suppression rate (SR), rSO2, CE, SpO2 and P(ET)CO2, in the following moments: M1 - before dexmedetomidine or 0.9% saline infusion; M2 - prior to intubation; M3 - following intubation; M4 - before incision; M5 - following incision; M6 - before CO2 inflation; M7 - following CO2 inflation; M8 - 10 min after CO2 inflation; M9 - 10 min after M8; M10 - 20 min after M8; M11 - 30 min after M8; M12 - 40 min after M8; and M13 - at emergence. Time for emergence and hospital discharge were also recorded. RESULTS: Dexmedetomidine has decreased sevoflurane end-expiratory concentration from M4 to M13 (p<0.05) when comparing Group I and Group II. No clinically significant changes were observed in hemodynamic parameters. Time for emergence in Groups I and II was 11 +/- 0.91 min. and 6.35 +/- 0.93 min., respectively (p < 0.05). Time for hospital discharge was 7.45 +/- 0.69 h in Group I and 8.37 +/- 0.88 h in Group II (p < 0.05). CONCLUSIONS: Dexmedetomidine was effective in decreasing sevoflurane end-expiratory concentration while maintaining hemodynamic stability without impairing time for hospital discharge, in addition to promoting an earlier emergence. PMID- 19475209 TI - Fresh-gas flow sequence at the start of low-flow anesthesia: clinical application of Maplesons theoretical study. AB - BACKGROUND AND OBJECTIVES: In a theoretical study, Mapleson using a multicompartmental pharmacokinetic model in a standard 40-year old and 70 kg man, has shown that with a fresh gas flow (FGF) initially equal to total pulmonary minute ventilation and then decreased to 1 L min(-1), and with fractional anesthetic administration (F(adm)) set to 3 MAC, the end fractional expired also expressed as alveolar (F(E')=F(A)) may reach 1 MAC in few minutes, according to the solubility of the inhaled agent. The purpose of this study was to clinically apply. METHODS: Twenty-eight patients of both genders, aged 18 to 55 years, scheduled to undergo general anesthesia, were randomly divided in four groups of seven patients each according to the anesthetic drug to be used (halothane, isoflurane, sevoflurane and desflurane). Anesthesia was induced with intravenous propofol, fentanyl and vecuronium, and maintained with the inhalational agent diluted in oxygen under mechanical ventilation. Gas parameters were set, according to the agent as follows: Halothane group: initial FGF of 5 L min(-1) up to the 4th minute, followed by 2.5 L min(-1) up to the 10th minute and 1.5 L min( 1) up to the 20th minute; F(adm) was 3 MAC during the first 20 minutes of anesthesia. Isoflurane group: initial FGF of 5 L min(-1) for 1.5 minute, followed by 1.5 L min(-1) up to the 7th minute and 1 L min(-1) up to the 20th minute. F(adm) was 3 MAC up to the 7th minute and 2.5 MAC up to the 20th minute. Sevoflurane group: initial FGF of 5 L min(-1) for 1 minute and 1 L min(-1) up to the 20th minute. F(adm) was 3 MAC for 1 minute, 2.5 MAC up to 7 minutes and 1.8 MAC up to the 20th minute. Desflurane group: initial FGF of 3.5 L min(-1) for 1 minute and 1 L min(-1) up to the 20th minute. F(adm) was 3 MAC for 1 minute followed by 1.5 MAC up to the 10th minute and 1.2 MAC up to the 20th minute. In addition to routine monitoring of physiological (cardiovascular and respiratory) variables, FI and FE (FA) of the inhaled agents were measured. RESULTS: Halothane group: FA reached 1.15 MAC in 2 minutes and varied from 1.21 to 1.47 MAC until the 20th minute. Isoflurane group: FA reached 1.03 MAC in 1 minute and varied from 1.11 to 1.21 MAC until the 20th minute. Sevoflurane group: FA reached 1.53 MAC in 1 minute and varied from 1.10 to 1.34 MAC until the 20th minute. Desflurane group: FA reached 0.94 MAC in 1 minute and varied from 1.07 to 1.14 MAC until the 20th minute. CONCLUSIONS: Results obtained confirm the clinical feasibility of Maplesons theoretical model. This way, a fast FA increase of the inhaled agent was achieved, which reached 1 MAC in 1 to 2 minutes and was maintained within this value with minor variations and low anesthetic consumption. PMID- 19475210 TI - Thoracic epidural anesthesia with ropivacaine for plastic surgery. AB - BACKGROUND AND OBJECTIVES: Thoracic epidural blockade is a method of hypotensive anesthesia able to reduce bleeding during surgery. This non-comparative study aimed at evaluating the results of thoracic epidural blockade with 0.5% ropivacaine associated to propofol continuous infusion sedation in plastic surgery. METHODS: Participated in this study 60 female patients aged 18 to 62 years, physical status ASA I or II, scheduled for combined plastic surgeries of breast, abdomen, gluteus and liposuction. After epidural puncture in T9-T10 or T10-T11, patients received 40 ml of 0.5% ropivacaine and 15 microg sufentanil. Additional local anesthetic doses were administered through an epidural catheter, if necessary. Sedation was induced with 40 to 50 microg kg(-1) min(-1) propofol continuous infusion. Blockade installation and regression, hemodynamic and respiratory parameters and the incidence of adverse effects were investigated. RESULTS: Upper sensory block level was T2 in 52 patients (86.6%), C4 in 4 (6.6%), and T3 in 4 (6.6%). Mean onset time was 9.1 +/- 8.2 min. Motor block grade 2 was obtained in 61.7% of patients, and grade 1 in 38.3%. Mean time for complete motor block regression was 377.9 +/- 68.5 min. Mean time for first spontaneous pain complaint was 965.1 +/- 371.3 min. SBP, DBP, MBP and HR mean values have significantly decreased as compared to control as from 15 min after local anesthetic injection, thus characterizing hypotensive anesthesia. Thirteen patients (21.7%) with SBP < 65 mmHg and/or MBP < 50 mmHg received a vasopressor (ethylphedrine) and 4 patients (6.7%) with HR < 50 bpm received atropine. No patient needed blood transfusion. CONCLUSIONS: Thoracic epidural blockade with 0.5% ropivacaine and 15 microg sufentanil associated to propofol continuous infusion sedation is a satisfactory hypotensive anesthesia technique for combined plastic surgeries involving breast, abdomen, gluteus and liposuction. Continuous monitoring of hemodynamic and respiratory parameters as well as controlling blockade effects on those parameters are critical for the success and safety of the technique. PMID- 19475211 TI - Patient controlled analgesia with fentanyl or sufentanil in the postoperative period of knee ligament reconstruction: comparative study. AB - BACKGROUND AND OBJECTIVES: Epidural opioids, associated or not to local anesthetics, have been used for postoperative analgesia in continuous infusion and/or patient controlled boluses. The aim of this study was to compare postoperative analgesia provided by epidural fentanyl or sufentanil, in bolus or continuous infusion, in patients submitted to knee ligament reconstruction. METHODS: Seventy ASA I - II patients, aged 16 to 47 years, were randomly distributed in two groups. All patients were submitted to epidural anesthesia with 0.5% bupivacaine (100 mg) with epinephrine 1:200,000 associated to fentanyl (100 mg). At the end of the procedure, patients received epidural fentanyl (Group F) or sufentanil (Group S) in continuous infusion plus patient controlled boluses. Group F infusion solution was made of saline (85 ml), 500 microg fentanyl (10 ml) and 0.5% bupivacaine (5 ml). Group S solution was made of saline (92 ml), 150 microg sufentanil (3 ml) and 0.5% plain bupivacaine (5 ml). Infusion pump's flow was initially programmed to 5 ml h(-1), with 2 ml patient controlled bolus doses every 15 minutes at most, for both groups. The following parameters were compared: pain, number of patient controlled boluses, opioid consumption, motor block, sedation and side-effects. RESULTS: There have been no statistically significant difference in analgesia quality between groups, being in most cases rated good (AVS 0 to 2). There has been a significant difference in the number of patient controlled boluses, with Group F needing more boluses than Group S. There has been no difference in total infused solution volume and total infusion time. There has been no motor block after beginning of patient-controlled analgesia. Vomiting and urine retention incidences were higher in Group S and there have been no significant differences in sedation and pruritus between groups. CONCLUSIONS: Epidural fentanyl or sufentanil in continuous epidural infusion and patient-controlled boluses in the doses used in this study have induced excellent postoperative analgesia. However, sufentanil caused more severe side effects than fentanyl. PMID- 19475212 TI - Postoperative analgesia in pediatric patients: comparative study among local anesthetics, opioids and non-steroidal anti-inflammatory drugs. AB - BACKGROUND AND OBJECTIVES: The treatment of postoperative pain in children has been given special attention in the last decades. This study aimed at analyzing postoperative analgesia in children, considering analgesia quality and duration, evaluation methods reliability and the incidence of side effects resulting from different analgesia techniques. METHODS: Participated in this study 100 children, aged 2 to 12 years, allocated in 5 groups of 20 children each, who received, right after anesthesia, the following analgesics: group B, 0.25% bupivacaine with epinephrine (1:400,000) 0.5 to 1 ml kg(-1); group F, 1.5 microg kg(-1) fentanyl; group M, 30 microg kg(-1) morphine; group S, 0.3 microg kg(-1) sufentanil, all by epidural caudal block and group D, who received rectal diclofenac (1 mg kg(-1)). Pain was evaluated by two different methods: one, predominantly behavioral and objective and the other subjective and self-evaluated, during the first 4 hours and then up to the 24th hour. Side effects were observed and treated. RESULTS: In the first 4 hours, groups B, F, M and S patients presented similar behavior, with a minimum need for complementary analgesia. In the remaining 20 hours, the longest analgesia duration was seen in group S, which did not differ from groups F and M, but was significantly longer than for groups B and D. Rectal diclofenac has not promoted effective pain relief. There has been a higher incidence of side effects in group M, which did not differ from group S, but was significantly higher than for groups F, B and D. There has been a positive and significant correlation between both pain scales. CONCLUSIONS: Spinal opioids are safe and effective for postoperative analgesia in children, but when compared to bupivacaine, there have been no significant differences and a higher incidence of side effects. Rectal diclofenac was not effective as a single analgesic as compared to other techniques. PMID- 19475213 TI - Onset time and duration of rocuronium, atracurium and mivacurium in pediatric patients. AB - BACKGROUND AND OBJECTIVES: Neuromuscular blockers (NMB) are widely used in pediatric anesthesia, but there is no ideal NMB. This study aimed at evaluating onset and recovery time, hemodynamic changes and tracheal intubation conditions of rocuronium, atracurium and mivacurium in pediatric patients. METHODS: Participated in this study 67 children aged 30 months to 12 years, physical status ASA I and II, who were allocated into three groups: G1 = 0.9 mg kg(-1) rocuronium (n = 22); G2 = 0.5 mg kg(-1) atracurium (n = 22); G3 = 0.15 mg kg(-1) mivacurium (n = 23). Anesthesia was induced with 50 microg kg(-1) alfentanil, 3 mg kg(-1) propofol, sevoflurane and N2O/O2. Neuromuscular block was monitored by acceleromyography on the ulnar nerve pathway. The following parameters were evaluated: onset time (OT), clinical duration (T25) relaxation time (T75) and recovery time (T(25-75)). Heart rate (HR) and mean blood pressure (MBP) were recorded in 6 moments, as well as tracheal intubation conditions. RESULTS: Median OT was: G1 = 0.6 min, G2 = 1.3 min, G3 = 1.9 min. Median T25 was: G1 = 38 min, G2 = 41.5, G3 = 8.8 min. Median T75 was: G1 = 57.7 min; G2 = 54.6 min, G3 = 13.6 min. Median T(25-75) was: G1 = 19.7 min, G2 = 13.1 min and G3 = 4.8 min. Tracheal intubation conditions were excellent for most children in all groups. There were no significant MBP and HR clinical changes. CONCLUSIONS: Rocuronium (0.9 mg kg( 1)) had the fastest onset time and mivacurium (0.15 mg kg(-1)) the shortest recovery time in pediatric patients anesthetized with sevoflurane. Rocuronium, mivacurium and atracurium had also not determined significant hemodynamic changes and allowed for excellent tracheal intubation conditions. PMID- 19475214 TI - Temperature and acid-base balance in coronary bypass grafting with cardiopulmonary bypass, under hypothermia and normothermia. AB - BACKGROUND AND OBJECTIVES: Cardiopulmonary bypass (CPB) is related to several changes in normal physiology. The multiple causes of these changes interact and are a potential risk for postoperative organic dysfunction. This study aimed at investigating changes in acid-base and metabolic balance during cardiopulmonary bypass with hypothermia and at comparing them to those observed in patients submitted to normothermal cardiopulmonary bypass. METHODS: Participated in this study 30 adult patients of both genders, aged 41 to 78 years, scheduled for coronary bypass grafting with CPB, under normothermia or hypothermia. The following parameters were evaluated: hemoglobin and blood gases concentration, pH, bicarbonate, base excess, anion gap, lactate ion, tissue oxygenation parameters and flow and systemic vascular resistance. RESULTS: There were no statistically significant differences in arterial pH, arterial bicarbonate, Na+ and Cl- plasma concentrations, anion gap, carbon dioxide partial pressure and arterial oxygen content between Normothermia and Hypothermia Groups. A time effect was observed for all variables except for base excess and anion gap. Base excess and K+ concentration were lower in the hypothermia group. Serum lactate increased in both groups when comparing time before CPB to after CPB, with higher levels in the hypothermia group. CONCLUSIONS: Mild hypothermia does not seem to substantially change acid-base balance as compared to normal temperature during CPB. Plasma lactate, however, has significantly increased in patients under hypothermia, suggesting inadequate oxygen transport to periphery during the proposed observation period. Low temperature, although mild, does not seem to offer the expected degree of cell protection to CPB blood flow. PMID- 19475215 TI - Arterial hypotension in myocardial revascularization surgery: influence of angiotensin-converting enzyme inhibitors. AB - BACKGROUND AND OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEI) are widely used in hypertension and heart failure. Their prolonged use may lead to hemodynamic instability and hypotension during anesthetic induction. This study aimed at comparing the incidence of hypotension in patients chronically treated and non treated with ACEI, submitted to anesthesia for myocardial revascularization. METHODS: Participated in this study 50 patients, physical status ASA II, III and IV, who were distributed in two groups: Group 1 - patients treated with ACEI for more than two months. Group 2 - patients not treated with ACEI. Parameters evaluated were mean blood pressure (MBP), heart rate (HR), and analysis of the ST segment in D(II) and V5. Systemic vascular resistance was determined during CPB. RESULTS: The incidence of arterial hypotension in anesthetized patients under ACEI was higher than in the control group in several anesthetic moments, but was predominant during anesthetic induction. This group needed dopamine for longer periods. From the 26 patients previously treated with ACEI, 23% needed drugs to correct hypotension from induction to CPB, and 19.1% in other anesthetic periods, totaling 42.3%. No control group patient needed drug infusion to increase systemic blood pressure, from induction to CPB. However, 21% of patients in this group needed dopamine or araminol in one or more anesthetic moments. CONCLUSIONS: In our study, patients treated with ACEI for prolonged periods had a higher incidence of hypotension on anesthetic induction, requiring more drugs to maintain systemic pressure in adequate levels. PMID- 19475216 TI - Preanesthetic clinical problems of morbidly obese patients submitted to bariatric surgery: comparison with non-obese patiens. AB - BACKGROUND AND OBJECTIVES: Morbid obesity is associated to clinical problems responsible for decreased life expectancy. Morbidly obese patients are candidates to gastric bypass and pose new challenges to the anesthesiologist. This study compared the prevalence of clinical problems among morbidly obese patients submitted to bariatric surgery to non-obese patients submitted to other elective surgical procedures. METHODS: Electronic records of 2986 patients were retrospectively studied. Patients were divided in two groups; 1: patients with morbid obesity submitted to bariatric surgeries; and group 2: non obese patients (body mass index less than 30 kg m(-2)), submitted to other elective surgical procedures. Groups were matched according to age, gender and ASA physical status. Preanesthetic problems common to group 1 were investigated in group 2, and prevalence was compared. Odds ratios and 95% confidence limits were calculated. RESULTS: Clinical problems identified in groups 1 and 2 and their respective prevalence were: gastroesophageal reflux (16.67% and 0.48%), systemic hypertension (50% and 3.06%), type II diabetes mellitus (6.25% and 0.31%), hypothyroidism (6.25% and 0.31%), bronchial asthma (10.42% and 1.43%) and restrictive lung disease (10.42% and 0.03%). Incidences were significantly higher in group 1. Additionally, the following problems were found in group 1, but not in group 2: epilepsy (2.08%), nonalcoholic fatty liver (12.5%), gall bladder stones (6.25%), dyslipemia (20.83%) and hypopytuitarism (2.08%). CONCLUSIONS: The prevalence of clinical problems was significantly higher in morbidly obese patients as compared to their non-obese counterparts. PMID- 19475217 TI - Histopathologic study on the effects of tenoxicam with bidistilled water or with 0.9% sodium chloride in rabbits venous endothelium. AB - BACKGROUND AND OBJECTIVES: After exposure to indomethacin, human umbilical vein endothelial cells have shown increased procoagulant activity. Thrombosis in rabbit auricular veins has been observed after injection of tenoxicam with its diluent or of the diluent alone. Human studies evaluating venous endothelium after tenoxican injection were not found in the literature. This study aimed at evaluating whether tenoxicam with 0.9% sodium chloride changes the venous endothelium of rabbits as it is observed when associated to its diluent (bidistilled water). METHODS: The study involved 90 rabbits (2000 and 3500 grams) divided in two groups: Control group, which received 0.9% NaCl; Experimental group, which received tenoxicam (20 mg) with bidistilled water or with 0.9% NaCl. A constant volume of 2 ml was administered to both groups. Anesthesia was induced with acepromazine maleate, ketamine hydrochloride and xylazine hydrochloride, and the puncture of right and left caudal auricular veins was performed with a 27G butterfly needle. Animals were confined for 6 hrs, 12 hrs, and 24 hrs, when they were once more anesthetized and sacrificed, with extraction of the auriculae at their base, followed by microscopic venous study. RESULTS: Thrombosis was observed in 19.4% of the Experimental Group after the administration of tenoxicam with bidistilled water and in 22.2% after the administration of tenoxicam with 0.9% sodium chloride. In the Control group, which has only received 0.9% sodium chloride, no thrombosis was observed. CONCLUSIONS: It was possible to conclude that tenoxicam, either with bidistilled water or 0.9% sodium chloride, has induced thrombosis in the veins it was injected. PMID- 19475218 TI - Marked hypercapnia during cardiopulmonary bypass for myocardial revascularization. Case report. AB - BACKGROUND AND OBJECTIVES: Bypassing heart blood and returning it oxygenated to systemic circulation is achieved at the expenses of major cardiopulmonary physiologic changes. The aim of this report was to present an anesthetic complication during CPB and to warn for the need of interaction of the whole anesthetic-surgical team to prevent adverse perioperative events. CASE REPORT: A brown female patient, 56 years old, 95 kg, height 1.65 m, physical status ASA IV, with chronic renal failure under hemodialysis was admitted for myocardial revascularization. Monitoring consisted of ECG, invasive blood pressure, pulse oximetry, capnography, esophageal temperature, central venous pressure and anesthetic gases analysis. Patient was premedicated with intravenous midazolam (0.05 mg kg(-1)). Anesthesia was induced with fentanyl (16 microg kg(-1)), etomidate (0.3 mg kg(-1)) and pancuronium (0.1 mg kg(-1)), and was maintained with O2, isoflurane (0.5 - 1 MAC) and fentanyl continuous infusion. Blood gas analysis after induction has shown: pH: 7.41; PaO2: 288 mmHg; PaCO2: 38 mmHg; HCO3: 24 mmol L(-1); BE: 0 mmol L(-1); SatO2 100%. A second blood gases analysis, sampled soon after CPB, returned in 30 minutes, showing: pH 7.15; PaO2: 86 mmHg; PaCO2 224 mmHg; HCO3: 29 mmol L(-1); BE: -3 mmol L(-1); SatO2 99%. Thorough and urgent checking of anesthetic and perfusion equipment was performed and revealed that the gas blender was connected to the O2 line and to a CO2 cylinder, when it should be connected to the compressed air cylinder. CONCLUSIONS: Bypass circuit mechanical problems may occur in the intraoperative period, and demand prompt repairs. Technological advances in anesthesia equipment, monitoring and safety standards will lessen the possibility of cases such as this to be repeated, but will never replace anesthesiologists surveillance. PMID- 19475219 TI - Pulmonary embolism in the operating room. Case report. AB - BACKGROUND AND OBJECTIVES: Pulmonary embolism is a common postoperative complication. This report aimed at presenting a case of pulmonary embolism in the operating room and at calling the attention to the importance of venous thrombosis prophylaxis in surgical patients. CASE REPORT: The authors describe a case of a male patient, 55 years of age and 83 kg submitted to radical prostatectomy for prostate cancer. At the end of the surgery and already extubated, patient presented hemodynamic instability and a decrease in SpO2 to 80%. Patient was re-intubated and sent to the ICU. CT images suggested pulmonary embolism. Patient died in the 5th postoperative day. CONCLUSIONS: A high suspicion rate is not enough to establish a diagnosis because pulmonary embolism is a silent disease and its investigation routine is not highly sensitive. Early prophylaxis is the best strategy. PMID- 19475220 TI - Postanesthetic delirium. AB - BACKGROUND AND OBJECTIVES: Postanesthetic Delirium (PAD) is a common acute mental disorder most commonly developed in elderly patients. Its pathophysiology is poorly understood and PAD is often confused with others psychiatric disorders. This study aimed at reviewing important features of this anesthetic complication in geriatric patients. CONTENTS: Postanesthetic delirium pathophysiological mechanisms, diagnosis and treatment are described. CONCLUSIONS: Postanesthetic delirium is a frequent and severe complication for geriatric patients. Little attention has been given to PAD and few prospective studies have been carried out. There are no available epidemiological studies on this subject in Brazil, nonetheless routine observation of geriatric patients admitted to postanesthetic care units and wards shows that PAD is a common event, suggesting the need for better preoperative assessment, adequate perioperative care and early diagnosis and treatment. PMID- 19475221 TI - [The influence of sevoflurane and isoflurane on the recovery from cisatracurium induced neuromuscular block.]. AB - BACKGROUND AND OBJECTIVES: The effects of neuromuscular blockers on the neuromuscular junction are potentiated by volatile anesthetics. This study aimed at evaluating the influence of sevoflurane and isoflurane on the recovery of cisatracurium- induced neuromuscular block. METHODS: Ninety ASA I and II patients undergoing elective surgeries under general anesthesia were included in this study. Patients were allocated in three groups: Group I (sevoflurane), Group II (isoflurane) and Group III (propofol). All patients were premedicated with intramuscular midazolam (0.1 mg.kg-1) 30 min before surgery. Anesthesia was induced with alfentanil (50 microg.kg-1), propofol (2.5 mg.kg-1) and cisatracurium (0.15 mg.kg-1). Patients were then ventilated under mask with 100% O2 until disappearance of all TOF responses when laryngoscopy and tracheal intubation were performed. Volatile agents for anesthetic maintenance were introduced immediately after tracheal intubation in 2% and 1% concentrations, respectively, for sevoflurane and isoflurane, as well as the propofol continuous infusion (7 to 10 mg.kg-1.h-1) for Group III. All patients received a 50% mixture of O2 and N2O. Neuromuscular function was monitored by adductor pollicis muscle acceleromyography with TOF stimulation at 15-second intervals. Clinical duration of neuromuscular block (T1(25%)) and recovery index (RI=T1(25-75%)) were evaluated. RESULTS: Mean time and standard deviation for clinical duration (T1(25%)) and recovery index (RI=T1(25-75%)) were respectively: Group I (66.2 +/- 13.42 min and 23.6 +/- 5.02 min), Group II (54.4 +/- 6.58 min and 14.9 +/- 3.82 min) and Group III (47.2 +/- 7.43 min and 16.2 +/- 2.93 min). There were significant differences in clinical duration between Groups I and II, I and III and II and III. There was a significant difference in recovery index between Group I and the other groups. CONCLUSIONS: The recovery from cisatracurium induced neuromuscular block was longer during anesthesia with volatile agents as compared to propofol. The most pronounced effect was observed with sevoflurane. PMID- 19475222 TI - [Dexmedetomidine and sufentanil as intraoperative analgesics: comparative study.]. AB - BACKGROUND AND OBJECTIVES: The use of alpha2-agonists to control heart rate and blood pressure, to attenuate hemodynamic responses to tracheal intubation and extubation and to reduce anesthetics requirement are already well established in the literature since clonidine introduction for therapeutic use. Dexmedetomidine, recently approved for clinical use, presents more alpha2-adrenergic receptors selectively, and therefore less adverse effects combined with marked analgesic and sedative properties. This has raised the interest in using it to replace opioids, known for their potent analgesic and sedative properties. This study aimed at comparing dexmedetomidine and sufentanil analgesias during continuous infusion for ENT, head and neck procedures. METHODS: Sixty patients were randomly distributed in two groups of 30: G1 - sufentanil and G2 - dexmedetomidine, for anesthetic induction and maintenance. Nitrous oxide and propofol in a target controlled continuous infusion were also used for anesthetic maintenance. The following parameters were evaluated: hemodynamic variables (systolic, diastolic blood pressure and heart rate), emergence and extubation times after propofol withdrawal, place where patients were extubated (operating room - OR, or post anesthetic recovery unit - PACU), PACU stay, Aldrete Kroulik index, and OR or PACU complications. RESULTS: G1 had lower systolic and diastolic blood pressure, lower heart rate values, longer emergence and extubation times, higher number of PACU extubations, longer PACU stay, lower Aldrete-Kroulik index and higher number of peri and postoperative complications. CONCLUSIONS: Dexmedetomidine as intraoperative analgesic was more effective as compared to sufentanil in the procedures selected for this study regarding hemodynamic stability, emergence and anesthetic recovery conditions. PMID- 19475223 TI - [Association of fentanyl or sufentanil an 0.5% isobaric bupivacaine in spinal anesthesia: a comparative study.]. AB - BACKGROUND AND OBJECTIVES: Since the discovery of opioid receptors and the increase in spinal cord neuropharma- cological knowledge as to transmission and inhibition of nociceptive stimulations, there has been an increased interest in spinal drugs for anesthesiology and pain relief. This study aimed at prospectively evaluating the clinical efficacy of fentanyl (25 microg) and sufentanil (5 microg) with isobaric bupivacaine (10 mg), in patients submitted to spinal anesthesia for varicose vein surgery. METHODS: Participated in this study 60 patients, physical status ASA I and II, aged below 60 years, submitted to spinal anesthesia for varicose vein sugery, who were randomly distributed in three groups: B (10 mg isobaric bupivacaine), BF (10 mg isobaric bupivacaine and 25 microg fentanyl) and BS (10 mg isobaric bupivacaine and 5 microg sufentanil). Spinal anesthesia was induced in the left lateral position; lumbar puncture was performed at L3-L4, with 27G Quincke needles. The following parameters were evaluated after spinal anesthesia: onset time, sensory and motor block level. The following parameters were recorded during the procedure: arterial hypotension, bradycardia, respiratory depression, oxygen hemoglobin peripheral saturation decrease, nausea, vomiting, pruritus and shivering. Analgesia duration was evaluated in the post-operative period. RESULTS: Groups were homogeneous. There were no significant differences in onset time, motor block and analgesia duration. There were differences in sensory block level between the control group and the opioid groups in all studied moments. Pruritus was the most frequent side effect in the opioid groups. CONCLUSIONS: The addition of fentanyl (25 microg) and sufentanil (5 microg) to isobaric bupivacaine (10 mg) in spinal anesthesia affects sensory block levels. PMID- 19475224 TI - [Unilateral spinal anesthesia with hypobaric bupivacaine.]. AB - BACKGROUND AND OBJECTIVES: Restricted sympathetic block during spinal anesthesia may minimize hemodynamic changes. In theory, the use of non-isobaric local anesthetics may induce unilateral anesthesia and limit sympathetic blockade to one side of the body. The local anesthetic dose and the time patients need to remain in the lateral position for achieving unilateral spinal anesthesia are not known. This prospective study investigated the incidence of unilateral spinal anesthesia following injection through a 27G Quincke needle of 0.15% hypobaric bupivacaine, prepared with 1.5 ml standard isobaric bupivacaine plus fentanyl (25 microg), in patients in the lateral position with the limb to be operated upwards. METHODS: Spinal anesthesia with 0.15% bupivacaine + fentanyl (25 microg) was induced through a 27G Quincke needle in 22 ASA I and II patients undergoing orthopedic surgery. Dural puncture was performed with the patient in the lateral position with the side to be operated upwards. After removal of 3 to 5 ml of CSF, 5 ml of the hypobaric bupivacaine-fentanyl mixture were injected at a speed of 1 ml.15 s-1. Sensory and motor block (pinprick/scale 0 to 3) were compared between operated and contralateral sides. RESULTS: Motor and sensory blocks in operated and contralateral sides were significantly different in all moments for both groups. Unilateral spinal anesthesia was obtained in 71% of the patients. No hemodynamic changes were observed in any patient. No patient developed post-dural puncture headache. CONCLUSIONS: Hypobaric 0.15% bupivacaine (7.5 mg) associated to fentanyl provided a predominantly unilateral block after twenty minutes in the lateral position. Major advantages of unilateral spinal anesthesia were hemodynamic stability, patient satisfaction and the absence of post-dural puncture headache. PMID- 19475225 TI - [Comparison of intravenous and epidural morphine analgesia after thoracotomy.]. AB - BACKGROUND AND OBJECTIVES: Patients undergoing thoracotomy experience severe postoperative pain. This study aimed at evaluating postoperative analgesia with the association of intravenous and epidural morphine as compared to a single route. METHODS: Participated in this study 20 patients of both genders, physical status ASA I, II or III, scheduled for thoracotomy. Patients were premedicated with intravenous midazolam (3 to 3.5 mg) in the OR. Monitoring consisted of continuous ECG, invasive blood pressure, pulse oximetry, capnography, CVP, diuresis and temperature. Continuous epidural anesthesia was induced in T7-T8 with 10 ml of 0.25% bupivacaine followed by fentanyl (5 microg.kg-1), etomidate(0.2 to 0.3 mg.kg-1) and succinylcholine (1 mg.kg-1). Tracheal intubation was performed with a double lumen tube and complemented with pancuronium(0.08 to 0.1 mg.kg-1) and mechanically controlled ventilation. Patients were then randomly distributed in three groups. Group I received 2 mg of 0.1% morphine by epidural catheter at anesthetic induction (M1), 12 h (M2) and 24 h (M3) after surgery. Group II received intravenous morphine by infusion pump (15 microg.kg.h-1) preceded by a 50 microg.kg-1 bolus, for 30 hours. Group III received 0.5 mg epidural morphine in M1, M2 and M3, associated to intravenous morphine by infusion pump (8 microg.kg.h-1), preceded by a 25 microg.kg-1 bolus, for 30 hours. Blood gas analysis, heart and respiratory rate, incidence of pruritus, nausea, vomiting and postoperative analgesia were evaluated at 6-hour intervals for 30 postoperative hours. Analgesia was evaluated by a numeric gradual scale (NGS) from 0 to 10. RESULTS: NGS was lower in Group I in M2, without differences in remaining intervals. Pain decreased in Groups II and III as from 18 hours as compared to baseline and to Group I. Group I needed more additional analgesia as compared to other groups. CONCLUSIONS: There has been a better analgesic effect with intravenous morphine or the association of intravenous and epidural morphine, with lower drug doses. This difference was significant when lower analgesic doses were used in these groups and represented an effective postoperative analgesic method for thoracotomy, with lower respiratory depression and emetic effects. PMID- 19475226 TI - [Residual analgesic effect of fentanyl in patients undergoing myocardial revascularization with cardiopulmonary bypass.]. AB - BACKGROUND AND OBJECTIVES: In spite of the frequent use of high doses of fentanyl for major surgeries, the correlation of its residual plasma concentration to postoperative analgesia deserves further investigation. This study aimed at evaluating the residual analgesic effect of fentanyl in the first and second postoperative days of myocardial revascularization, as well as quantifying its concentration. METHODS: Participated in this study 11 patients undergoing myocardial revascularization with cardiopulmonary bypass under general anesthesia with 50 microg.kg-1 intravenous fentanyl. Analgesia was evaluated by a numeric verbal scale at moments zero (extubation), 70 min, 3, 5, 8 and 12 hours in the first day; and moments zero (24 h after extubation), 70 min, 3, 5, 8 and 12 hours in second post-operative day. Pain intensity to vigorous cough and respiratory physical therapy was evaluated. At every measurement, patients were asked about the need for analgesic complementation. Plasma samples were collected in moments zero (extubation), 70 min, 3, 5, 8 and 12 hours during the first and second postoperative days for fentanyl radioimmunoassay. RESULTS: Mean pain intensity varied from 1.9 to 3.7 in the first day and from 2.1 to 3.8 in the second postoperative day. Fentanyl plasma levels (> 1 ng/ml) evidenced its contribution to post-operative analgesia during the first postoperative day. CONCLUSIONS: In spite of the lack of correlation between residual fentanyl plasma concentration and pain intensity, patients referred only mild pain during the whole investigation period. PMID- 19475227 TI - [Intra-articular analgesia with morphine, bupivacaine or fentanyl after knee video-arthroscopy surgery.]. AB - BACKGROUND AND OBJECTIVES: Methods to promote knee pain analgesia without impairing motor function have been widely researched. This study aimed at comparing intra-articular morphine, bupivacaine, and fentanyl analgesic effects (as compared to saline solution), after knee video-arthroscopy. METHODS: Participated in this study 60 patients who were randomly distributed in four groups: GI (n = 15) 10 ml saline solution; GII (n = 15) 2 mg morphine diluted in 10 ml saline solution; GIII (n = 15) 10 ml of 0.25% bupivacaine; GIV (n = 15) 100 microg fentanyl diluted in 10 ml saline solution, injected at surgery completion. All patients received spinal anesthesia with 15 mg hyperbaric bupivacaine. Pain intensity was evaluated by a visual analog scale (VAS) (at surgery completion, and 6, 12, 18 and 24 hours later). The need for analgesic complementation (1 g intravenous dipirone) was also evaluated. Side effects were recorded. RESULTS: There were no statistical differences in pain intensity among groups in almost all moments studied. There was a statistic difference up to 6 hours, when the fentanyl group had significantly lower pain. The morphine group needed more dipirone complementation. Side effects were minor, without statistical significance. CONCLUSIONS: There were no statistical differences among solutions analgesic effects in almost all moments studied. PMID- 19475228 TI - [Tomographic identification of popliteal nerves epineural sheath during foot intermittent regional anesthesia: case report.]. AB - BACKGROUND AND OBJECTIVES: Lower limb regional nervous blocks are common procedures for surgery and postoperative analgesia. This study aimed at describing a rare and casual tomographic image of a catheter in the popliteal fossa, which was originally directed to the sciatic nerve, and of anesthetic solution spread during intermittent analgesia for foot trauma. CASE REPORT: Male patient, 54 years old, physical status ASA III, with severe left foot trauma and submitted to sciatic nerve block through a catheter inserted in the apex of the popliteal triangle. Since 10 ml injections of 0.375% bupivacaine with epinephrine 1:400,000 allowed for daily dressings and debridement while preserving plantar sensitivity, the phenomenon was radiologically investigated. Enhanced radiographic and tomographic studies of the popliteal region were able to show catheter positioning and anesthetic spread under the sheath of each component of the sciatic nerve. CONCLUSIONS: Relevant enhanced tomographic findings of the popliteal region have proven a recent anatomic study on the individualization of the neural sheath involving popliteal nerves with implications in blockade outcome. Anesthesia obtained by a catheter in the popliteal fossa was effective only in the superficial fibular nerve dermatome (medial dorsum of foot and hallux). PMID- 19475229 TI - [Upper airway obstruction after peritonsillar abscess drainage: case report.]. AB - BACKGROUND AND OBJECTIVES: Peritonsillar abscess is an unusual complication, but predisposes to severe upper airway complications. This report aimed at presenting a case of upper airway obstruction after surgical drainage of a peritonsillar abscess in a healthy young female patient. CASE REPORT: Young female patient, 26 years old, with severe peritonsillar abscess and submitted to general anesthesia for drainage. After extubation, she presented a severe respiratory failure requiring reintubation and controlled ventilation for 24 hours. CONCLUSIONS: The anesthetic strategy and the adequate surgical indication are fundamental in preventing complications during ENT surgeries. PMID- 19475230 TI - [Anesthesiologists blood pressure during surgical anesthetic procedures in the morning.]. AB - BACKGROUND AND OBJECTIVES: Systemic arterial hypertension affects approximately 20% of the world population, depending on the interaction between genetic predisposition and environmental factors. Stresses inherent to the anesthesiologists work might reflect in the cardiovascular system, influencing professionals blood pressure. This study aimed at verifying whether the practice of anesthesia is a triggering factor for anesthesiologists blood pressure changes during surgical anesthetic procedures. METHODS: Participated in these study 10 anesthesiologists, each one inducing 10 spinal anesthesias for cesarean section. Blood pressure was measured in five different moments, in a total of 50 readings one each anesthesiologist. The first measure was recorded soon after the anesthesiologists arrival in the operating center and was called M1; the second, before lumbar puncture and was called M2; the third, immediately after needle removal from the puncture site and was called M3; the forth reading, M4, was obtained immediately after fetal extraction; and the last value, M5, at end of skin suture. RESULTS: There has been anesthesiologists blood pressure increase in moments M3 and M4. CONCLUSIONS: The anesthetic practice is responsible for significant changes in anesthesiologists blood pressure and is a direct function of moments of higher risk for the patient during surgical anesthetic procedures. PMID- 19475231 TI - [Electrocardiogram analysis by the anesthesiologist.]. AB - BACKGROUND AND OBJECTIVES: The primary goal of preoperative evaluation is to decrease morbidity/mortality related to surgical anesthetic procedures. All patients clinical surgical history must be obtained and only then the necessary exams may be determined. One of the most required exams is the electrocardiogram. This study aimed at comparing electrocar- diographic interpretation by cardiologists and different groups of anesthesiologists at Santa Casa de Porto Alegre. METHODS: Fifty resting electrocardiograms of several patients undergoing non cardiac surgeries were selected. All ECGs were analyzed and interpreted by two cardiologists and their agreement was considered the golden standard for interpretation. Anesthesiologists were divided in three groups: I - Preoperative Evaluation anesthesiologists - POEA (n = 5); II - Surgical Center Sarmento Barata Anesthesiologists (n = 10) and III - Resident Anesthesiologists (n = 5). All participants were asked to perform an ECG analysis and scores were established for such evaluation: rhythm = 2 points, heart rate = 1 point, P and PR = 2 points, QRS = 2 points, ST and T = 2 points and primary diagnosis = 1 point. RESULTS: Means obtained for each group were: group I - 7.35 +/- 0.86 points; group II - 5.44 +/- 1.69 points and group III - 6.34 +/- 0.89 points and the difference between groups I and II was statistically significant (p < 0.05). CONCLUSIONS: Preoperative Evaluation Anesthesiologists achieved a higher score as compared to other groups. This was probably related to more training obtained by the constant ECG interpretation in the clinic. PMID- 19475232 TI - [Dexmedetomidine: pharmacology and clinical application.]. AB - BACKGROUND AND OBJECTIVES: Dexmedetomidine is the newest alpha2-adrenergic agonist for clinical application. It has a fast onset, is metabolized by the liver and mostly excreted by the urine. This review aimed at presenting pharmacokinetic and pharmacodynamic profiles of dexmedetomidine and its clinical applications. CONTENTS: Dexmedetomidine pharmacokinetic and pharmacodynamic profiles are presented and compared to other alpha2-adrenergic agonist drugs, the prototype of which is clonidine. Cardiac, vascular, neurological and gynecologic procedure outcomes are commented. CONCLUSIONS: Dexmedetomidine is an innovative drug for sedation and analgesia. Its major qualities are fast onset and titration, allowing for changes in sedation and analgesia depth. In addition, it has a synergism with commonly used anesthetic drugs, with a low incidence of side effects and minor respiratory depression. PMID- 19475233 TI - [Complex regional pain syndrome: epidemiology, pathophysiology, clinical manifestations, diagnostic tests and therapeutic proposals.]. AB - BACKGROUND AND OBJECTIVES: The term Complex Regional Pain Syndrome (CRPS) was adopted as from 1994 by the International Association for Study of Pain (IASP) Consensus. It previously referred to by several other names, such as Reflex Sympathetic Dystrophy, Causalgia, Algodystrophy or Sudecks Atrophy, and is a disease where the understanding of clinical limits, pathophysiology and pathogenic implications is still very poor. Thus resulting in disappointment both for patients and for health professionals with regard to currently available therapies. This study aimed at reviewing the literature and updating information to improve the understanding of this severe painful syndrome. CONTENTS: This study is a literature review of several CRPS aspects, with emphasis in its causes, definition and taxonomy, pathophysiology, clinical characteristics, diagnostic tests and most recent therapies. CONCLUSIONS: There are few well controlled, double blind and randomized CRPS studies with large samples, and there are still several questions about this disease. The treatment is usually empirical and the patient outcome is poor. PMID- 19475234 TI - [Intrathecal drugs for chronic pain control.]. AB - BACKGROUND AND OBJECTIVES: Chronic pain is a challenge for modern medicine. New methods and drugs have been proposed to control pain. Intrathecal administration is a feasible and safe option, but still requires further investigations. This study aimed at reviewing available and well established drugs as well as new promising alternatives for the daily practice. CONTENTS: Several neuraxial drugs with analgesic action are reviewed. Desirable and undesirable effects of opioids, local anesthetics, alpha2-agonists, excitatory and inhibitory aminoacid antagonists, acetylcholine, acetyl-cholinesterase inhibitors, calcium channel blockers, adenosine, serotonin, tricyclic antidepressants and prostaglandin synthesis inhibitors are analyzed. CONCLUSIONS: Several advances were achieved in controlling pain with intrathecal administration of the above-mentioned drugs. Certainly some will be used, thus enriching therapeutic armamentarium, and others will be temporarily or permanently abandoned. However, several clinical and experimental studies will still be needed for knew knowledge to be incorporated and safely used by professionals dealing with chronic pain. PMID- 19475235 TI - [Opioids for treating non malignant chronic pain: the role of methadone.]. AB - BACKGROUND AND OBJECTIVES: The use of opioids for cancer pain has already well established by several well-controlled clinical trials. However, there is a major controversy about long-term use of opioids in non-malignant chronic pain, which has been significantly intensified in the last few years. This study aimed at evaluating available data on the use of opioids for treating non-malignant chronic pain and the role of methadone as a therapeutic alternative. CONTENTS: There are few available studies, but they show that some subpopulations of chronic pain patients may achieve sustained analgesia with minor tolerance and low addiction potential, mainly those refractory to conventional therapy. Morphine is the standard opioid, but other alternatives may be used such as oxycodone, hydromorphone or fentanyl. Methadone is a synthetic opioid, initially used to prevent withdrawal syndrome in addicted patients, which may be an important alternative for treating non-malignant chronic pain, especially neuropathic pain. CONCLUSIONS: Although the growing knowledge on the use of opioids for treating non-malignant chronic pain, new better controlled studies are still needed to allow a more scientific discussion about this subject. Oral methadone is cost-effective and an effective alternative for a better pain control in certain patients. PMID- 19475236 TI - [Spinal anesthesia with 0.5% hyperbaric ropivacaine and 0.5% hyperbaric bupivacaine: a comparative study.]. AB - BACKGROUND AND OBJECTIVES: Spinal anesthesia with ropivacaine has been proven safe both in experimental and clinical studies. On the other hand, ropivacaine is approximately half as potent as bupivacaine in spinal anesthesia when both drugs are used in hyperbaric solutions. This study aimed at comparing clinical spinal block features obtained with hyperbaric ropivacaine or bupivacaine in equipotent doses. METHODS: Twenty ASA I or II patients, aged 20 to 60 years, scheduled for elective surgeries of lower limbs, perineum and inguinal hernioplasty, were randomly allocated into two groups . Group R (n = 10) were given 4 ml 0.5% hyperbaric ropivacaine and Group B (n = 10) were given 2 ml of 0.5% hyperbaric bupivacaine intratecally. Puncture was performed with a 25G needle in the sitting position. Monitoring consisted of SBP, DBP, MBP, HR, ECG and SpO2. Sensory and motor block onset and recovery times, hemodynamic and respiratory changes, and the incidence of adverse effects were recorded. RESULTS: There were no differences between groups in demographics data, sensory block onset (174.4 +/- 75.9 vs. 191 +/- 51.7 s), motor block onset (373.6 +/- 214.6 vs. 240 +/- 60 s), upper level of sensory block T8 - T10 (90% of group R patients vs. 70% of group B), motor block grade 3 (50% of group R patients vs. 30% of group B), time to total sensory block recovery (178.5 +/- 65.2 vs. 181 +/- 26.9 minutes), time to total motor block recovery (192 +/- 50.7 vs. 162.5 +/- 37.8 minutes), and time for first spontaneous pain complaint (183.9 +/- 37.1 vs. 206.5 +/- 46.6 minutes). CONCLUSIONS: No differences in spinal block clinical features were observed between hyperbaric 0.5% ropivacaine and 0.5% bupivacaine, when administered in equipotent doses. Data seem to confirm previous observations that in these conditions, ropivacaines potency is approximately half bupivacaines potency. PMID- 19475237 TI - [Intramuscular versus rectal diclofenac associated with low dose spinal morphine for post-cesarean analgesia.]. AB - BACKGROUND AND OBJECTIVES: Diclofenac has been used in combination with spinal opioids to control postoperative pain; however, the best regimen of its administration is not known. This study evaluated the quality of postoperative analgesia of different regimens of diclofenac administration, in patients submitted to Cesarean section under spinal anesthesia with bupivacaine and morphine. METHODS: After the end of surgery, patients were randomly allocated into three groups that received diclofenac as follows: G50VR(n=62), 50 mg rectally; G50IM(n=62), 50 mg intramuscularly and G75IM (n=62), 75 mg intramuscularly. Pain was evaluated with a 0-10 cm visual analog scale (VAS) every 30 minutes for six hours and rescue intravenous (iv) meperidine was administered whenever VAS >/= 3 cm. RESULTS: In the interval between 30 and 150 min after diclofenac administration, mean pain scores in G50VR (0.9 +/- 1.4; 1.4 +/- 1.4; 1.3 +/- 1.5; 1.3 +/- 1.2 and 1.5 +/- 3.3 cm) were higher as compared to G50IM (0.4 +/- 0.8; 0.5 +/- 0.8; 0.7 +/- 1.0; 0.7 +/- 1.1 and 0.7 +/- 1.1cm) and G75IM (0.4 +/- 0.8; 0.7 +/- 1.3; 0.7 +/- 1.1; 0.8 +/- 1.2 and 0.7 +/- 1.0 cm). The need for rescue meperidine (43.5%) and total meperidine consumption (21.3 +/- 28.9 mg) were higher in G50VR as compared to G50IM (21% and 8.2 +/- 18.2 mg) and G75IM (19.4% and 6.8 +/- 16.7 mg) respectively. CONCLUSIONS: When associated with low doses of spinal morphine, intramuscular diclofenac offers better postoperative analgesia than the rectal route. Additionally, a ceiling effect is probably present for this drug, as no advantages were observed with doses larger than 50 mg intramuscularly. PMID- 19475238 TI - [Influence of propofol and etomidate on rocuronium-induced euromuscular block: evaluation with acceleromyography.]. AB - BACKGROUND AND OBJECTIVES: Some hypnotics may interact with neuromuscular blockers and potentiate their effects. This study aimed at evaluating the influence of propofol and etomidate on rocuronium-induced neuromuscular block. METHODS: Participated in this study 60 patients, physical status ASA I and II, scheduled for elective surgeries under general anesthesia, who were randomly distributed in two groups according to the hypnotic drug: Group I (propofol) and Group II (etomidate). All patients were premedicated with intramuscular midazolam (0.1 mg.kg-1), 30 minutes before surgery. Anesthesia was induced with propofol (2.5 mg.kg-1) or etomidate (0.3 mg.kg-1) preceded by alfentanil (50 microg.kg-1) and followed by rocuronium (0.6 mg.kg-1). Patients were ventilated under mask with 100% oxygen until achieving a decrease of 75% or more in the adductor pollicis muscle response amplitude. Neuromuscular function was monitored by accelerometry. The following parameters were evaluated: rocuronium onset (T1 <= 25%); time for complete neuromuscular block; neuromuscular block degree at tracheal intubation; tracheal intubation conditions and hemodynamic effects. RESULTS: Complete rocuronium-induced neuromuscular block onset times (in seconds) were: Group I (48.20 +/- 10.85 s and 58.87 +/- 10.73 s) and Group II (51.20 +/- 13.80 s and 64.27 +/- 18.55 s). Neuromuscular block degree at tracheal intubation was: Group I (77.50%) and Group II (76.96%). Tracheal intubation conditions were satisfactory in 100% of Group I patients and in 83.33% of Group II patients. There has been a significant decrease in mean blood pressure, followed by an increase after hypnotic injection, in both groups. CONCLUSIONS: Propofol and etomidate had a similar behavior regarding time for rocuronium-induced neuromuscular block and tracheal intubation conditions. PMID- 19475239 TI - [Comparison of ophthalmic periconal blockade with 1% and 0.75% ropivacaine with lateral infraorbital and medial canthus punctures.]. AB - BACKGROUND AND OBJECTIVES: Several drugs and methods are used for peribulbar blockade. Our objective was to investigate the quality of ophthalmic periconal blockade by the double puncture technique, with different ropivacaine concentrations and without hyaluronidase. METHODS: Participated in this study fifty patients submitted to ophthalmologic surgery, who were randomly allocated in two groups: R1 (1% Ropivacaine) and R0.75 (0.75% Ropivacaine). Local anesthetic volume was adjusted according to the tole- rance and elasticity of the periconal space at the infraorbital site and, when necessary, not more than 3 ml were used at the medial canthus site. Motor function scores were attributed to each rectus muscle. Motor block of the levator palpebrae superioris and orbicularis muscles was also evaluated. Data were evaluated in the following moments: M0 = immediately before blockade; M5 = 5 minutes after blockade; M 10= 10 minutes after blockade; and M15 = 15 minutes after blockade. RESULTS: Two R1 patients and eight R0.75 patients needed complementation and this difference was significant. In 72% of cases only 2 initial punctures were performed in both groups. Total anesthetic volume and first puncture volume were, respectively, for R1: 9.72 +/- 2.38 ml and 6.96 +/- 0.97 ml; and for R0.75: 12.64 +/- 5.10 ml and 7.36 +/- 1.07 ml, also with significant differences. There were significant motor function score differences in moments M10 (R1 = 1.6; R0.75 = 3.8) and M15 (R1 = 1.04; R0.75 = 2.8). CONCLUSIONS: We concluded that 1% ropivacaine is more effective than 0.75% ropivacaine when no hyaluronidase is used to perform ophthalmic periconal blockade by the double puncture technique. There was a trend to less punctures with 1% ropivacaine and a significantly lower number of patients needed complementation in this same group. PMID- 19475240 TI - [Evaluation of pulmonary function in patients undergoing cardiac surgery with cardiopulmonary bypass.]. AB - BACKGROUND AND OBJECTIVES: Pulmonary complications are still a major postoperative problem for cardiac surgeries with cardiopulmonary bypass (CPB). This study aimed at evaluating pulmonary function changes in patients undergoing myocardial revascularization, as compared to those submitted to valve replacement. METHODS: Participated in this study patients undergoing myocardial revascularization (MR Group, n=15) and valve replacement (VR Group, n=15) who were evaluated by the ratio between oxygen blood pressure and its inspired fraction (PaO2/FiO2), oxygen alveolar-arterial gradient (GA-aO2), pulmonary shunt, best compliance PEEP and static PEEP, evaluated in the preoperative period, after anesthetic induction, 1, 3 and 6 postoperative hours and 1st and 2nd postoperative days. Data were analyzed by analysis of variance for repeated measures (p < 0.05). RESULTS: Alveolar-arterial gradient and pulmonary shunt results were significantly higher for the MR group as compared to the VR group. PaO2/FiO2 ratio was significantly higher in the VR group. There were no differences between groups in static compliance. Postoperative best compliance PEEP was significantly higher in the MR group as compared to the VR group. CONCLUSIONS: Our study has shown that patients submitted to myocardial revascularization presented pulmonary function changes different from those submitted to valve replacement. PMID- 19475241 TI - [Airflow resistance of double-lumen tracheal tubes.]. AB - BACKGROUNG AND OBJECTIVES: Double lumen tubes may determine different flow resistances. This disparity may result in non-homogeneous ventilation. This study aimed at comparing the resistive pressure of 37 FR double lumen tubes to distinct flows as compared to conventional adult tracheal tubes. METHODS: Tracheal tubes with internal diameters of 7; 7.5; 8 and 8.5 millimeters (mm) and 37 FR double lumen tubes were tested. Flows were generated and maintained by a conventional anesthesia ventilator. Resistive pressure generated in the tubes was measured by a variable inlet pneumotachograph and converted to a digital system. Resistances were obtained by dividing measured pressures by flows. Data were submitted to analysis of variance (ANOVA) and Tukeys test. RESULTS: Five independent measurements were obtained. All tubes were opened to the environment. Resistances are shown in cmH2O.L-1.s-1. Resistance is linearly increased with increased flow. The 37 FR tube had a resistive pattern similar to the 7.5 mm tracheal tube. The occlusion of any double lumen branch significantly increases flow resistance. Flows set at 0.1 L.s-1 to 0.2 L.s-1 resulted in similar resistive pressures for all tubes, except for the 7 mm or the occluded 37 FR tube (p < 0.001). CONCLUSIONS: Resistive patterns of 37 FR and 7,5 mm tubes were very similar. Any double lumen branch occlusion significantly increases resistance, however in a similar way for both branches for flows below 0.5 L.s-1. These results suggest the use of low inspiratory flow to minimize ventilatory system resistive pressure when any branch of a double-lumen tube is occluded. PMID- 19475242 TI - [Anesthesia in glucose 6-phosphate dehydrogenase-deficient patient: case report.]. AB - BACKGROUND AND OBJECTIVES: Glucose 6-phosphate dehydrogenase (G6PD) deficiency is a relatively common enzymopathy, but there are few publications relating such condition to anesthesia. This report aimed at presenting a case of a G6PD deficient patient, submitted to Achilles tendon tenotomy under intravenous anesthesia associated to spinal block. CASE REPORT: Male patient, 9 years old, 48 kg, with G6PD deficiency and peripheral polineuropathy, submitted to Achilles tendon tenotomy under general intravenous anesthesia with midazolam, propofol and fentanyl, associated to spinal block with 0.5% hyperbaric bupivacaine. At surgery completion patient awakened relaxed, without pain or other complaints, had a good evolution and was discharged without intercurrences. CONCLUSIONS: According to the evolution of this case, spinal anesthesia with bupivacaine associated to total intravenous anesthesia with propofol has shown to be a safe technique for G6PD-deficient patients. PMID- 19475243 TI - [Epidural patch with dextran 40 to prevent postdural puncture headache in an HIV patient: case report.]. AB - BACKGROUND AND OBJECTIVES: Postdural puncture headache is a well-known complication of spinal and epidural anesthesia and, so far, its most effective treatment is the epidural blood patch. Nevertheless this is an invasive procedure subject to severe complications. Its use in special patient populations (HIV positive patients and leukemias) is controversial. Several alternatives have been reported. This study aimed at showing a case of prophylactic epidural dextran 40 patch in an HIV patient with previous history of headache following spinal anesthesia. CASE REPORT: Male patient, 31 years old, 70 kg, physical status ASA II, HIV positive, presented for recurrent anal condylomatosis treatment, with a history of severe and limiting headache for two weeks following spinal anesthesia. (25G Quincke needle). During an L3-L4 epidural puncture attempt with an 18G Tuohy needle there was an accidental dural puncture. Twenty milliliters of 10% dextran 40 were administered twice through an epidural catheter. First, 150 minutes after anesthesia and then in the morning following surgery. Patient had no headache complaint and was discharged on the following day. CONCLUSIONS: The use of a patch with colloid solutions, such as dextran 40, is not well established, but there are some successful reports and it is our understanding that its potential should be further investigated. PMID- 19475244 TI - [Retrospective study of anesthetic deaths in the first 24 hours: review of 82,641 anesthesias.]. AB - BACKGROUND AND OBJECTIVES: Since the first reported anesthetic death, many attempts have been made to study the incidence of risk factors, complications and mortality associated to anesthesia and surgery. The estimated perioperative mortality risk varies from 0.05 to 10 cases per 10,000 anesthesias. This study aimed at reporting the incidence of anesthetic-surgical death in the first 24 hours, at our hospital. METHODS: Charts had been reviewed from 82,641 surgeries performed in 1998 and 1999. Deaths were analyzed according to Edwards classification, and by age, gender, physical status, (ASA), type of surgery and anesthesia. RESULTS: Cause of the deaths according to Edwards classification has shown that 91.04% were class V, 3.77% class VI, 2.13% class VII, 2.84% class IV and 0.23% were class I. Age above 65 years accounted for 1.48% of deaths; adults incidence was 0.48%; the incidence in children aged 1 to 12 years was 0.11%; in children aged 31 days to 1 year it was 1.29% and in neonates up to 30 days of life the incidence was 2.88%. Death ratio as compared to total deaths was 59.2% in adults, 30.2% in patients above 65 years of age, 2.8% at the age 1 to 12, 4% in patients with 31 days of life to 1 year and 3.8% in newborn babies. Males represented 66.3% of deaths and females 33.7%. The distribution by ASA physical status was: ASA I - 11.1%, ASA II - 5.2%, ASA III - 30.9%, ASA IV - 34.4% and ASA V - 18.4%. Emergency surgeries accounted for 67.2% of deaths and elective surgeries for 32.8%. General incidence of the deaths was 0.51% being the highest in cardiac (1.88%) and vascular (1.87%) surgeries. CONCLUSIONS: Anesthetic surgical deaths in the years 1998 and 1999 were considered inevitable according to Edwards classification. The highest incidence of deaths was in neonates. Most deaths occurred in males, ASA III or above patients, and emergency vascular or cardiac surgeries. PMID- 19475245 TI - [Management of perioperative bronchospasm.]. AB - BACKGROUND AND OBJECTIVES: The prevalence of asthma is increasing and anesthesiologists may start seeing this clinical manifestation more often in the perioperative period. This study aimed at investigating different bronchospasm management techniques during anesthesia. METHODS: A questionnaire was mailed to a stratified sample of 108 anesthesiologists from the Anesthesiology Society of State of Sao Paulo (SAESP). Questions involved individual bronchospasm statistics and management, clinical evolution, professional experience and the management of patients with upper airway infection (UAI). RESULTS: After mailing three stratified samples (324 questionnaires), 73 questionnaires were returned with a reported bronchospasm incidence of 0.90%. Management techniques were: steroids (90.41%), halogenates (68.49%), teophylline (50.68%), inhalational beta2-agonists (47.95%) and epinephrine (41.10%). Most anesthesiologists would discontinue general (84.93%) or regional anesthesia (64,38%) in UAI patients. CONCLUSIONS: The diversity of reported treatments indicate the need for spreading international protocols on asthma treatment and control, emphasizing the specific use of inhalational beta2- agonists and steroids. PMID- 19475246 TI - [Postoperative analgesia in children less than 1 year of age: a retrospective analysis.]. AB - BACKGROUND AND OBJECTIVES: Postoperative pain is still a major complication causing discomfort, especially for children. This study aimed at evaluating the use of analgesics from surgery completion to postoperative intensive care unit (PACU) discharge as a prophylactic or therapeutic approach for children less than 1 year of age. METHODS: Based on the Anesthesiology Department files, a retrospective analysis was performed with children less than 1 year of age submitted to different surgical procedures from January/2000 to April/2001, to evaluate postoperative analgesia-related aspects. RESULTS: During the study period, 402 children aged less than 1 year were anesthetized. From those, 194 (48.2%) were not medicated with analgesics and 208 (51.8%) were. As to using or not analgesics, the following was observed: Without analgesics: (1) Age: up to 1 month, 68/99; between 1 and 6 months, 53/126; from 6 months to 1 year, 73/177. (2) Weight: 6.7 +/- 3.1 kg. (3) Gender: male, 106/240; female, 88/162. (4) ASA Physical Status: ASA I, 69/187; ASA II, 56/113; ASA III, 46/79; ASA IV, 23/23. (5) Caudal anesthesia: 3/4. (6) Anesthesia duration: 106 +/- 32 minutes. (7) Referral to intensive care unit (ICU): 93/119. With analgesics: (1) Age: up to 1 month, 31/99; between 1 and 6 months, 73/126; from 6 months to 1 year, 104/177. (2) Weight: 9 +/- 2.3 kg. (3) Gender: male, 134/240; female, 74/162. (4) ASA Physical Status: ASA I, 118/187; ASA II, 57/113; ASA III, 33/79; ASA IV, 0/23. (5) Caudal anesthesia: 1/4. (6) Anesthesia duration: 130 +/- 38 minutes. (7) Referral to ICU: 26/119. Analgesic drugs used were: dipyrone (60.6%), dipyrone + tramadol (25.5%), dipyrone + nalbuphine (5.3%), tramadol (3.8%), nalbuphine (3.8%), meperidine (0.5%) and fentanyl (0.5%). CONCLUSIONS: Analgesics prescription for children, from surgery completion to PACU discharge, was not usual, especially in younger and more severely ill children and in shorter surgical procedures. Dipyrone, alone, and the association dipyrone/tramadol were the most frequent drugs used. PMID- 19475248 TI - [Ventilation in anesthesia: a retrospective study.]. AB - BACKGROUND AND OBJECTIVES: Lung mechanics impairment, Functional Residual Capacity decrease and atelectasis have been described during general anesthesia. This study aimed at retrospectively evaluating ventilation standards in place at the Central Institute, Hospital das Clinicas, Medical School, University of Sao Paulo (HCFMUSP). METHODS: Data on 240 patients under general anesthesia, neuromuscular block and mechanical ventilation were recorded. Ventilation standards - tidal volume in ml (VT), respiratory rate per minute, airway pressure in cmH2O, fresh gas flow in L.min-1, SpO2 and P ET CO2 - were recorded, as well as gender, age, weight and height. Body mass index (BMI) was calculated and patients were distributed in four groups: BMI < 20; 20-25; 25-30 and > 30 kg/m(2). RESULTS: There has been a linear correlation between tidal volume (VT) and weight (r=0.640), and BMI (r=0.467). VT by body mass (ml.kg-1) has shown to be inversely related to BMI: BMI < 20 with 10.74 +/- 1.39; BMI 20-25 with 9.67 +/ 1.08; BMI 25-30 to 8.54 +/- 1.09; BMI > 30 to 7.86 +/- 1.26 (p < 0.001, ANOVA). There have been no differences among groups in respiratory rate. During data collection, males (n = 123) and females (n = 117) had similar SpO2 and P ET CO2, as well as BMI. Positive end-expiratory pressure (PEEP) was installed in 78 procedures (33%). CONCLUSIONS: These descriptive data allow us to state that mechanical ventilation standards in anesthesia at HCFMUSP use a tidal volume close to 9 ml.kg-1 and a respiratory rate of 10 incursions per minute. PEEP is not widely applied, but when installed it is approximately 4 cmH2O. Weight and BMI had a positive correlation with VT, and VT/weight (ml.kg-1) ratio was inversely related to BMI. PMID- 19475247 TI - [Clinical experience with sedatives in the intensive care unit: a retrospective study.]. AB - BACKGROUND AND OBJECTIVES: Among the most frequent indications for Intensive Care Unit patients sedation, one may mention artificial ventilation installation and maintenance, anxiety and uncomfortable or painful procedures. This retrospective study aimed at evaluating most common sedation indications and techniques for severe patients admitted to the Surgical Intensive Care Unit, Escola Paulista de Medicina (EPM/UNIFESP) during an 11-month period. METHODS: After excluding patients remaining in the ICU for less than 24 hours and those without the necessary evaluation to determine their severity index (APACHE II), the sample was reduced to 307 patients. Most common techniques, sedation indications and neuromuscular blockers association were evaluated. RESULTS: Sedation was administered to 37.4% of patients. Psychiatric disorders, such as delirium, agitation, fear and anxiety, were some indications for sedation and corresponded to 25.77% of all indications. Most ventilated patients also needed sedative agents and mechanical ventilation installation and maintenance represented most indications, or approximately 57.73% of all sedated patients. Procedures, such as tracheal intubation and bronchoscopy, represented 11.34% of all indications and metabolic control (barbiturate coma and tetanus) represented 5.15% of the cases. Most common sedative techniques included opioids alone or associated to benzodiazepines. In this study, fentanyl alone was used in 58% of the cases, and fentanyl plus midazolam in 21.64% of patients. Haloperidol, diazepam, propofol and thiopental added up 19.5%. Neuromuscular blockers were used in 22.7% of mechanically in ventilated patients. CONCLUSIONS: Sedation is a common therapeutic resource for intensive care and is widely used to help mechanical ventilation and to treat psychiatric disorders. Fentanyl, alone or in association with midazolam, was the most widely used agent. PMID- 19475249 TI - [Simplified sciatic nerve approach by the posterior route at the median gluteus femoral sulcus region, with a neurostimulator.]. AB - BACKGROUND AND OBJECTIVES: The sciatic nerve may be blocked by several routes, all of them with advantages and disadvantages. It is the largest human nerve in diameter and length, being the prolongation of the upper sacral plexus fascicle (L4, L5, S2 and S3). It leaves the pelvis through the foramen ischiadicum majus, passing below the piriform muscle and going down between the greater trochanter and the ischial tuberosity, continuing along the femoral dorsum, anterior to biceps femoris and semitendinous muscles, to the lower femoral third, where it is divided in two major branches called tibial and common fibular nerves. It becomes superficial at the lower border of the gluteus maximus muscle. Based on this anatomic description, we developed a posterior approach with the following advantages: easy identification of the surface anatomy, superficial level of the nerve at this location; and less discomfort to patients since a 5 cm needle may be used. METHODS: Seventeen ASA I - III patients aged 21 to 79 years, weighing 55 to 90 kg, undergoing leg or foot surgery were studied. After monitoring, patients were placed in the prone position and blockade was performed at the middle point of the sulcus gluteus (skin fold between nates and posterior thigh), with the aid of a neurostimulator, using 1% plain lidocaine (300 mg). Onset time, blockade performing time, and tibial, common fibular and cutaneous femoris posterior nerves anesthesia were evaluated. Saphenous nerve was also blocked with 5 ml of 1% lidocaine whenever needed. RESULTS: Adequate anesthesia was obtained in all cases. There was no patient with cutaneous femoris posterior nerve anesthesia. Blockade performing time was 8.58 +/- 5.71 min. Onset time was 5.88 +/- 1.6 min. Sensory and motor block duration was 4.05 +/- 1.1 and 2.9 +/- 0.8 hours, respectively. CONCLUSIONS: This new approach is effective and easy. However, it is not indicated when the cutaneous femoris posterior nerve anesthesia is necessary. PMID- 19475250 TI - [Dawning of inhalational anesthesia: a historical perspective.]. AB - BACKGROUND AND OBJECTIVES: History, unlike one may imagine, is not something unchangeable and limited to the past. It is adapted according to conveniences of one or other ruling social class. Deliberately or accidentally hidden information, when unveiled may change current concepts, so far taken for granted. So, history, as any other science, is not totally impartial; it suffers influences and interferences of political, religious, economic and cultural thinking. The same is true for anesthesia. Some questions remain unanswered: Why did it take so long for the civilization to control pain? Who did in fact discover Anesthesia? How was the world when Anesthesia was officially discovered? To discuss such questions it is necessary to go back to the History of Anesthesia. CONTENTS: This paper addresses the surgical act, pain and anesthesia from the Hellenic culture to the first officially recognized anesthesia, often emphasizing forgotten names and historical peculiarities which have benefited or harmed one or other discoverer. It also focuses on values, culture and scientific developments of the 19th century, correlating them to events that marked the dawning of anesthesia. CONCLUSIONS: It would be unfair to attribute the merit of discovering anesthesia to a single person. Historical peculiarities that benefited or harmed one or other researcher cannot be forgotten. Morton was undoubtedly the most favored by the circumstances. He lived in a privileged time and place and has met the most adequate people to his intent. However there is still a question. After all, who is the most important: the father of the idea or who disclosed it? The answer will certainly remain in the field of subjectivity. PMID- 19475251 TI - [Evaluation of electroencephalographic parameters during the administration of different nitrous oxide concentrations.]. AB - BACKGROUND AND OBJECTIVES: Spectral electroencephalography has been used to measure anesthetic depth, hypnosis and sedation levels induced by different anesthetic agents. This study aimed at evaluating the effects of N2O on electroencephalographic (EEG) variables and sedation levels according to Observer Assessment of Alertness/Sedation (OAA/S) scale, as well as on hemodynamic and respiratory parameters. METHODS: Thirty adult patients from both genders, physical status ASA I, aged 20 and 40 years, were submitted to the following protocol: after 10 minutes of relaxation, spontaneously breathing with eyes close, patients were given 30% and 50% N2O concentrations under face mask. Data were collected in three moments: M1- before N2O administration; M2 - 30% N2O in O2; M3 - 50% N2O in O2. Data for M2 and M3 were collected 15 minutes after stabilization of 30% and 50% N2O expired fractions (FeN2O), respectively, with a 5-minute interval between fractions. The following parameters were evaluated: electroencephalographic: BIS, SEF1, SEF2, power energy (PE) and burst suppression (BS); hemodynamic: heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP); respiratory: oxygen hemoglobin saturation (SpO2), carbon dioxide expired pressure (P ET CO2), minute ventilation and respiratory rate; clinical: patients were rated in a descending order (5, 4, 3, 2 and 1) according to OAA/S scale. RESULTS: N2O administrated at 30% and 50% concentrations has statistically changed BIS, SEF1, SEF2, PE and OAA/S level of sedation in the studied moments. No clinically important changes were observed, as all patients were cooperative and slightly sedated, though SEF1 and SEF2 indications of deep hypnosis. Hemodynamic and respiratory parameters changes were not statistically significant. CONCLUSIONS: N2O at 30% and 50% concentrations in non-premedicated patients has induced mild sedation according to OAA/S scale. There has been correspondence with BIS, but not with SEF1 and SEF2. PMID- 19475252 TI - [Priming versus bolus: a comparative study with different cisatracurium doses.]. AB - BACKGROUND AND OBJECTIVES: The priming technique is an alternative to shorten nondepolarizing neuromuscular blockers onset time. This study aimed at evaluating maximum neuromuscular block onset, tracheal intubation conditions and cardiocirculatory changes determined by different cisatracurium single or fractional doses. METHODS: Participated in this study 80 patients physical status ASA I and II, who were distributed into two groups according to cisatracurium doses: Group I (0.1 mg.kg-1) and Group II (0.2 mg.kg-1). Subgroups were constituted according to the curarization technique employed: subgroups P1 and P2 (priming-dose) - 0.02 mg.kg-1 or 0.04 mg.kg-1cisatracurium, respectively, followed one minute later, by 0.08 mg.kg-1 or 0.16 mg.kg-1 of the same neuromuscular blocker, respectively; subgroups U1 and U2 - total bolus injection of 0.1 mg.kg-1 or 0.2 mg.kg-1 cisatracurium, respectively. Anesthesia was induced with etomidate, preceded by alfentanil. Train of Four (TOF) stimulation was applied at 12-second intervals to monitor neuromuscular function. Maximum neuromuscular blockade onset time, tracheal intubation conditions and changes in hemodynamic parameters (arterial mean blood pressure and heart rate) were evaluated. RESULTS: Mean times for maximum neuromuscular block onset were: Group I (3.90 +/- 0.60 min and 3.88 +/- 0.74 min, for subgroups P1 and U1, respectively) and Group II (1.40 +/- 0.40 min and 2 +/- 0.30 min, for subgroups P2 and U2, respectively) with no significant differences. Comparison between subgroups P1 and P2 and between subgroups U1 and U2, has shown statistically significant differences. Tracheal intubation conditions were acceptable in all patients and there were no cardiovascular changes. CONCLUSIONS: Fractional cisatracurium doses have not shortened maximum neuromuscular block onset as compared to bolus injections. They have however produced acceptable tracheal intubation conditions without cardiovascular changes. PMID- 19475253 TI - [Evaluation of maternal acid-base status after different doses of spinal sufentanil for cesarean section and its effects on the neonates.]. AB - BACKGROUND AND OBJECTIVES: Spinal sufentanil in obstetric anesthesia promotes immediate pain relief, improves anesthesia quality and prolongs postoperative analgesia, its major side effect being respiratory depression. This study aimed at evaluating maternal acid-base status after different doses of spinal sufentanil associated to hyperbaric bupivacaine for cesarean section, and its effects on neonates' vitality. METHODS: Participated in this study 40 full term pregnant women, physical status I (ASA), aged 17 to 35 years, who were submitted to elective cesarean section under spinal anesthesia. Patients were distributed into two equal groups: Group I received 12 mg of hyperbaric 0.5% bupivacaine associated to 2.5 microg sufentanil; Group II received 12 mg of hyperbaric 0.5% bupivacaine associated to 5 microg sufentanil. The following parameters were evaluated: maternal acid-base status through arterial blood gas analysis before anesthesia and after birth, SpO2, hemodynamic changes, neonates' vitality evaluated through Apgar Index and umbilical cord blood gas analysis, in addition to the incidence of side effects. RESULTS: There were no differences between groups in all parameters evaluated, with a mild maternal metabolic acidosis compensated in both groups both before anesthesia and soon after birth, however without clinical repercussions. Neonates showed good vitality and normal blood gas analysis. CONCLUSIONS: The association of spinal hyperbaric 0.5% bupivacaine to low sufentanil doses has shown to be safe to both mother and neonate, preserving their hemodynamic and acid-base status. PMID- 19475254 TI - [Evaluation of low flow anesthesia, comparing pressure-controlled ventilation to time-cycled pressure-limited continuous flow ventilation: experimental model in rabbits.]. AB - BACKGROUND AND OBJECTIVES: Despite the well-known advantages of rebreathing systems and low flow anesthesia, they are seldom used in small animals and pediatric anesthesia. The experimental model of this study was designed to evaluate a rebreathing system with flows between 500 to 1,000 ml.min-1 in small animals, in addition to comparing time-controlled pressure-limited and constant gas flow ventilation to pressure-controlled ventilation in a new anesthesia machine. METHODS: Sixteen female rabbits were randomly allocated in two groups (GI and GII), anesthetized with halothane and submitted to mechanically controlled ventilation. Adjustments in ventilatory parameters were allowed in GI (peak inspiratory pressure, respiratory rate and inspiratory time) to maintain normocapnia, tidal volume between 6 and 8 ml.kg-1 and arterial pH between 7.35 and 7.45. Adjustments in GII were only allowed at control moment. RESULTS: Carbon dioxide rebreathing was observed in both groups when rebreathing systems were evaluated, regardless of the ventilation mode. Arterial pH was maintained within physiologic parameters in GI, and respiratory acidosis was observed in GII when the rebreathing system was evaluated during pressure-controlled ventilation. CONCLUSIONS: According to our results, a circle system with flows between 500 and 1,000 ml.min-1 may be an alternative for low weight patients anesthesia, provided necessary monitoring is performed. Ventilation efficiency was primarily a function of adjusted ventilatory parameters, of airways compliance and resistance and not so much of the ventilation mode. PMID- 19475255 TI - [Total intravenous anesthesia for thymectomy in a Myasthenia Gravis patient: case report.]. AB - BACKGROUND AND OBJECTIVES: Patients with neuromuscular diseases, as Myasthenia Gravis, react abnormally to anesthetics, depending on the technique and on the drugs. This report aimed at showing a case of Myasthenia Gravis patient submitted to thymectomy under total intravenous anesthesia with propofol and remifentanil. CASE REPORT: Female Myasthenia Gravis patient, 52 years old, 72 kg, submitted to transternal thymectomy, under total intravenous anesthesia with propofol in target controlled infusion (3 microg.ml-1) and continuous remifentanil (0.3 microg.kg-1.min-1). Succinylcholine (50 mg) was used for tracheal intubation, which was achieved without difficulty. Tramadol (50 mg), ketoprofen (100 mg) and dipirone (1 g) were used for postoperative analgesia. Propofol and remifentanil were withdrawn at surgery completion and patient was extubated 15 minutes after. Patient was eupneic, awaken, without pain, moving limbs, with respiratory frequency of 14 mpm and 97% oxygen saturation. Patient remained in the Intermediate Care Unit for 36 hours, with a nasal catheter of 2 L.min-1 O2 and was discharged in the 4th postoperative day. CONCLUSIONS: Total intravenous anesthesia, with short-lasting anesthetics without active metabolites has favored recovery and early extubation of a Myasthenia Gravis patient submitted to thymectomy. PMID- 19475256 TI - [Anesthesia in patient with Xeroderma Pigmentosum: case report.]. AB - BACKGROUND AND OBJECTIVES: Xeroderma Pigmentosum is a rare, autosomal recessive disease characterized by the premature development of neoplasias due to an exacerbated hypersensitivity to UV radiation. These manifestations are due to DNA excision and repair mechanism damage. As compared to normal individuals, these patients have a 1000-fold increased risk for developing neoplasias on sun-exposed areas. This report aimed at describing the anesthetic management of a patient with Xeroderma Pigmentosum submitted to ophthalmologic surgery. CASE REPORT: Female patient, 7 years of age, with Xeroderma Pigmentosum and extensive facial involvement, submitted to right eye papillomatous lesion excision. Patient was premedicated with 10 mg oral midazolam. Initial monitoring consisted of cardioscope, pulse oximetry, precordial stethoscope and noninvasive blood pressure. Patient was preoxygenated with 100% oxygen for 3 minutes and inhalational anesthesia was induced with sevoflurane under mask in incremental concentrations up to 7%. Peripheral venous access was achieved with a 22G catheter followed by intravenous 50 mg propofol and 20 mg succinylcholine and tracheal intubation with a 5.5 mm uncuffed tracheal tube. A guide wire was used to help tracheal tube introduction. Anesthesia was maintained with 3,5% sevoflurane and 100% oxygen with Bain's Circuit. Patient was extubated in the operating room and was sent to the post-anesthetic care unit in good conditions. CONCLUSIONS: Facial and oropharyngeal changes caused by this pathology have imposed many difficulties for facial mask adaptation and tracheal intubation. Patient and relatives continuous education are the most important Xeroderma Pigmentosum management objective. PMID- 19475257 TI - [Anesthesia for orthopedic surgery in a child susceptible to malignant hyperthermia: case report.]. AB - BACKGROUND AND OBJECTIVES: Malignant hyperthermia is an autosomal dominant myopathy triggered by inhalational anesthetics and neuromuscular blockers, such as halothane and succinylcholine, which causes temperature increases that may be fatal if not promptly treated. This report aimed at describing anesthesia in a child susceptible to malignant hyperthermia submitted to orthopedic surgery. CASE REPORT: Female patient, 3 years of age, with congenital hip dislocation and susceptible to malignant hyperthermia, according to anesthetic history, who was submitted to corrective orthopedic surgery under general anesthesia with propofol and fentanyl, combined with lumbar epidural anesthesia. Temperature was closely monitored during surgery and in the postoperative period. Postoperative recovery was uneventful and patient was discharged five days later. CONCLUSIONS: Combined regional and intravenous anesthesia for the surgical procedure proposed to a patient susceptible to malignant hyperthermia allowed a safe anesthetic approach. PMID- 19475258 TI - [Arterial air embolism during anesthesia for percutaneous pulmonary node location: case report.]. AB - BACKGROUND AND OBJECTIVES: Arterial air embolism is a complication that may occur during several surgical procedures and is associated to a high morbidity and mortality rate. This report aimed at presenting a case of arterial air embolism during general anesthesia for percutaneous CT-guided location of a pulmonary node. CASE REPORT: Male patient, 33 years old, physical status ASA II, was submitted to percutaneous location of a pulmonary node (probably a femoral giant cell tumor metastasis) with the hook-wire technique under general anesthesia. Anesthesia was induced without difficulties and the procedure was started with the patient in the right lateral position. After hook insertion, while the surgeons checked its positioning with CT images, arterial hypotension and bradycardia followed by asystole was observed. Cardiopulmonary resuscitation maneuvers, thoracic drainage and transthoracic echocardiography were performed. The presence of air in the descending aorta was seen at a later CT image. Cardiac arrest was reversed 15 minutes after resuscitation maneuvers. Patient was referred to the ICU and discharged 6 days later without sequelae. CONCLUSIONS: Arterial air embolism is a complication of different procedures most of them performed with the patient under general anesthesia. Anesthesiologists must be prepared to recognize involved problems and make the differential diagnosis. Suitable and adequate treatment is critical to decrease morbidity and mortality associated to this event. PMID- 19475259 TI - [Exercise-induced rhabdomyolysis and risk for malignant hyperthermia: case report.]. AB - BACKGROUND AND OBJECTIVES: Rhabdomyolysis is a skeletal muscle injury with cell components' release to plasma. Exhaustive exercise, especially in non-conditioned individuals, may result in severe morbidity such as hyperkalemia, metabolic acidosis, disseminated intravascular coagulation, acute respiratory distress syndrome and rhabdomyolysis. It has been suggested that malignant hyperthermia, thermal shock and exercise-induced rhabdomyolysis are closely related syndromes. This report aimed at describing a case of fatal rhabdomyolysis after physical exercise and its correlation with malignant hyperthermia. CASE REPORT: Male patient, 32 year-old, presented with discomfort followed by syncope after running 2,350 m in a fitness race. Patient was taken to the hospital, evolved with respiratory failure, bradyarrhythmia, arterial hypotension and cardiac arrest, being resuscitated. Nevertheless, patient became comatose with severe muscle stiffness, persistent shock, coagulation problems, metabolic acidosis, hyperkalemia and died less than 24 hours later. Autopsy findings revealed rhabdomyolysis-induced acute pulmonary edema, disseminated intravascular coagulation and acute renal failure. CONCLUSIONS: It has been suggested that malignant hyperthermia and exercise-induced rhabdomyolysis are closely related syndromes. Patient died before any specific investigation of malignant hyperthermia, but it is important to look for susceptibility for this syndrome within the family to avoid potentially life-threatening anesthetic events. PMID- 19475260 TI - [Patient controlled analgesia in a university hospital.]. AB - BACKGROUND AND OBJECTIVES: The rapid development seen in recent years in surgical and anesthetic techniques allowed for an increased indication of invasive procedures. At the same time, with the aging of the population, the postoperative recovery period became the focus of major concern for the healthcare team. For such, new analgesic techniques were developed, among them, Patient Controlled Analgesia (PCA). In Brazil, the Acute Pain Service (SEDA) of the Anesthesiology Department, Botucatu Medical School - UNESP, has been using PCA for many years. Aiming at verifying the quality of the service provided, this research has evaluated the efficacy and safety of the technique, in addition to identifying and characterizing patients submitted to PCA. METHODS: Participated in this retrospective study 679 patients treated by SEDA with the PCA method only, during a 3-year period. Patients were randomly included in the study with no restrictions concerning age, gender and type of surgery, considering only the possibility of PCA. The following parameters were evaluated: gender, age, type of surgery, pain score, treatment duration, analgesic drugs used, administration route, side effects and complications. RESULTS: The PCA technique was used in 3.96% of patients submitted to surgical procedures and in 1.64% of all hospitalized patients. Thoracic surgeries were the most frequent procedures and accounted for 25% of patients. Morphine was the most commonly used analgesics (54.2%) and the epidural route was the most frequent route of administration. Mean verbal numeric scale was 0.8 (0-10), and side effects were present in 22.4% of treated patients. CONCLUSIONS: Results were considered excellent in terms of quality of analgesia, although with the incidence of some side effects. The PCA technique was widely accepted by the medical specialties of the hospital. PMID- 19475261 TI - [Outpatient preoperative evaluation and clients' satisfaction.]. AB - BACKGROUND AND OBJECTIVES: Increasingly, anesthesiologists are performing preoperative evaluation. This study aimed at transversally evaluating external and internal clients satisfaction with Santa Casa de Porto Alegre outpatient preoperative evaluation department (APOA). METHODS: A questionnaire was applied for one month to external clients (patients) before and after evaluation, and internal clients (anesthesiologists and surgeons) to evaluate their satisfaction with the preoperative evaluation department. RESULTS: Ninety-nine percent of patients, 97% of anesthesiologists and 76% of surgeons were happy with the service. CONCLUSIONS: Major issues were identified through clients suggestions and were primarily related to process logistics and to the difficulties of other anesthesiologists in accepting preoperative approaches based on APOAs clinical and epidemiological evidences. PMID- 19475262 TI - [Latex allergy.]. AB - BACKGROUND AND OBJECTIVES: Latex products very present in the Anesthesiology practice. The first latex allergy report dates from 1933. The incidence of latex sensitivity among anesthesiologists is 12.5% to 15.8%. It increases in some specific groups leading to dangerous reactions and even to lethal cases. The purpose of this study was to review literature on such important subject to the anesthesiologist, addressing diagnosis, prevention, and treatment of latex allergy. CONTENTS: Studies on the prevalence of latex allergy differ a lot because different populations are evaluated with different methods to establish the sensitivity to the antigen. In spite of those variations there are some very high-risk groups, especially disabled children with neural tube defects. Clinical presentations vary from cutaneous eruptions to anaphylaxis and death. Early diagnosis with IgE evaluation may prevent such reactions. CONCLUSIONS: The early diagnosis of latex allergy is critically important. Dealing with these patients in latex-free environments prevents sensitization and, very often, the evolution to dramatic situations. PMID- 19475263 TI - [Dexmedetomidine in anesthesiology.]. AB - BACKGROUND AND OBJECTIVES: Dexmedetomidine is a new alpha2-adrenergic agonist with a selectivity ratio of 1600:1 (alpha2:alpha1). It has important sedative and analgesic effects, good hemodynamic control at stress situations and may, by itself, induce anesthesia. This drug has been used to promote postoperative and intensive care sedation and analgesia. Due to such properties, dexmedetomidine has recently become a co adjuvant drug for anesthesia. So, this is a review of the literature about dexmedetomidine in anesthesia. CONTENTS: Major studies on dexmedetomidine in Anesthesiology are presented, both as premedication and during anesthesia. Action mechanisms of alpha2-adrenergic agonists and dexmedetomidine pharmacokinetic and pharmacodynamic properties are also reviewed in this paper. CONCLUSIONS: Dexmedetomidine premedication, infusion during anesthesia or in the postoperative period improves hemodynamic stability. Anesthetic consumption is decreased during anesthesia. Patients sedated with dexmedetomidine may awake, when requested and become cooperative. Even high dexmedetomidine doses do not cause respiratory depression. Bradycardia is a frequent side effect which may be minimized by slow drug infusion. So, dexmedetomidine is an important additional resource to anesthetic practice that may be used in different patients and surgical procedures. PMID- 19475264 TI - [Preoperative assessment of lung disease patients.]. AB - BACKGROUND AND OBJECTIVES: Lung complications are the most frequent causes of postoperative morbidity-mortality, especially in lung disease patients. So, those patients should be preoperatively carefully evaluated and prepared, both clinically and laboratorially. This review aimed at determining surgical risk and at establishing preoperative procedures to minimize peri and postoperative morbidity-mortality in lung disease patients. CONTENTS: Major anesthetic-surgical repercussions in lung function have already been described. Similarly, we tried to select higher-risk patients, submitted or not to lung resection. To that end, clinical and laboratorial propedeutics were used. Finally, a proposal of a preoperative algorithm was presented for procedures with lung resection. CONCLUSIONS: Lung disease patients, especially those with chronic evolution, need to be preoperatively thoroughly evaluated. ASA physical status and Goldmans cardiac index are important risk forecasting factors for lung disease patients not candidates for lung resection. Adding to these criteria, estimated postoperative max VO2, FEV1 and diffusion capacity are mandatory for some patients submitted to lung resection. beta2-agonists and steroids should be considered in the preoperative period of these patients. PMID- 19475266 TI - [Not Available]. PMID- 19475265 TI - [Nine Biblical anesthetic premises.]. AB - BACKGROUND AND OBJECTIVES: The authors produced a historical analysis of nine anesthesia-related premises described in the Bible more than 3,500 years ago (Old Testament). Anesthetic drugs and adjuvants, patients, anesthesiologists attitudes and techniques are discussed in the light of Biblical and modern science. CONTENTS: To help understanding, the nine premises evaluated are correlated to the book of Bible citation: I - Jehovah, the pioneer of inhalational anesthesia - Gen 2; II - Alcoholic hypnosis and anesthesia - Prov 20, Gen 19, Marc 15; III - Anesthesia-related Chaos and Chronobiology - Gen 1, Ecles 3; IV - Anesthetic drugs Stereoisomerism - Ecle 42, Gen 1; V - Elijah s and Elisha s cardiopulmonary resuscitation - Gen 2, Kings III 17, Kings IV 4; VI - Tocoanalgesia - Gen 3, Rev 12, Gen 35 and Rachels post-partum death - Ex 1; VII - Jehovah s witnesses interpretation of blood transfusion forbiddance - Lev 7,17; VIII - Acidosis for epileptic seizure treatment - Math 17; IX - Death on the cross by hypovolemic shock - Marc 15, John 19. CONCLUSIONS: According to the anesthetic premises discussed, Holy Bible reading without fundamentalism shows no incompatibility between religion, science and anesthesia, except for Jehovah,s witnesses interpretation of Leviticus VII-XVII, by which they would lose eternal life because transfused blood is an impure food forbidden by Jehovah. PMID- 19475267 TI - [Electroneourophysiological changes in anesthesia with sevoflurane: comparative study between healthy and cerebral palsy patients.]. AB - BACKGROUND AND OBJECTIVES: There are very few studies on anesthetic drugs pharmacodynamics in patients with Cerebral Palsy (CP). This study aimed at comparing electroneurophysiological responses in healthy and CP patients, using bispectral index (BIS) and short-latency somatosensory evoked potential (SEP) to monitore sevoflurane-induced central nervous system (CNS) electroneurophysiological changes. METHODS: Twenty four patients aged 3 to 18 years, scheduled for surgical procedures were allocated in two groups: 1. CP - 12 patients with spastic CP; 2. Control (C) - 12 patients with no neurological disease. Anesthesia was induced with sevoflurane and 60% N2O in assisted ventilation. BIS and N9, N13, N19 and N/P22 SEP waveforms - amplitude and latency - were recorded at baseline and at 1.2% and 2.5% end-tidal sevoflurane concentration (ETsev), corresponding to 0.5 and 1 MAC, respectively. Monitoring consisted of temperature, ETsev and P ET CO2. For statistical analysis, BIS mean and standard deviation as well as means percentage variation of SEP waveforms latency and amplitude in both anesthetic concentrations, were used. RESULTS: There were no significant differences in gender, age, weight and temperature between groups. Under anesthesia, BIS values were lower in the CP group, whit statistical significance only at 2.5% ETsev (30.3 x 37.5; p < 0.05). Percentage SEP waveforms latency increase was higher in the CP group. CONCLUSIONS: Results suggest a deeper anesthetic depressing effect in the CP group and this difference was captured by BIS and SEP waves. PMID- 19475268 TI - [Continuous epidural anesthesia with 0.2% ropivacaine associated to general anesthesia for upper abdominal surgery in children.]. AB - BACKGROUND AND OBJECTIVES: Several anesthetic techniques have been proposed for different pediatric surgeries to promote postoperative analgesia, among other advantages. This study aimed at evaluating propofol infusion rate and postanesthetic recovery of children submitted to upper abdominal surgeries under epidural anesthesia with 0.2% ropivacaine associated to general anesthesia with propofol or propofol plus sufentanil. METHODS: Participated in this study 26 children physical status ASA I, II and III, aged 0 to 4 years, were scheduled to upper abdominal surgeries under thoracic epidural anesthesia (T7-T8) with 0.2% ropivacaine (1.5 ml.kg-1). They were randomly distributed in two groups: Propofol (propofol infusion) and Sufentanil (propofol infusion plus 1 microg.kg-1 sufentanil). Propofol infusion rates were 20 and 10 mg.kg-1.h-1 for the Propofol and Sufentanil groups, respectively, adjusted to maintain blood pressure in approximately 20% of baseline values and withdrawn 10 to 15 minutes before estimated surgery completion. Postanesthetic recovery was evaluated by a modified Aldrete-Kroulik scale and sedation was evaluated by a 5 grade score. RESULTS: Techical difficulties excluded two children of each group. Infusion rate was significantly slower in the Sufentanil group as compared to the Propofol group during 100 minutes after beginning of surgery. Time for extubation and referral to post-anesthetic recovery unit (PACU) was significantly shorter for the Propofol group, however sedation intensity and duration were longer in this group as compared to Sufentanil group. Recovery scores were similar for both groups. Three hours after PACU admission all patients were meeting criteria to be transferred to the ward. Transient arterial hypotension was observed in 2 Sufentanil group patients. CONCLUSIONS: Continuous thoracic epidural anesthesia with 0.2% ropivacaine (1.5 mg.kg-1) associated to propofol infusion provides effective and safe anesthesia for upper pediatric abdominal surgeries. Propofol infusion rate and sedation duration were decreased with the association of sufentanil. PMID- 19475269 TI - [Comparative study between 0.5% bupivacaine and 0.5% enantiomeric mixture of bupivacaine (S75-R25) in epidural anesthesia.]. AB - BACKGROUND AND OBJECTIVES: A bupivacaine formulation containing 25% of R(+) and 75% of S(-) isomer has been used because its anesthetic properties with less toxicity than the racemic bupivacaine. This study aimed at evaluating the racemic bupivacaine as compared to B25/75 in epidural anesthesia. METHODS: Participated in this study 44 patients who were distributed in two groups (n = 22), namely Bupivacaine and S75-R25. Patients were premedicated with intravenous midazolam. Epidural anesthesia was induced at L3-L4 or L2-L3 interspace with 16 to 24 ml of the anesthetic solution. Group Bupivacaine received 0.5% bupivacaine with vasoconstrictor. Group S75-R25 received the enantiomeric mixture of 0.5% bupivacaine with vasoconstrictor. The following parameters were evaluated: lower limb temperature before and after epidural block, blockade onset, type of sensation referred by the patient, possible sensory failures, metameric sensory level and motor block level. Time for first analgesic request in the PACU was also recorded. RESULTS: Forty-one patients completed the study. Groups were demographically similar. Perioperative midazolam dose, epidural anesthetic volume, blockade onset, sensory failures at pinprick, lower limb temperature in different moments, type of paresthesia sensation and anesthetic depth in dermatomes were similar between groups. Motor block was less intense in group S75 R25 (p = 0.0117) as compared to group Bupivacaine. Time to first postoperative analgesic dose was longer for group S75-R25 as compared to group Bupivacaine (596 +/- 436 min versus 463 +/- 270 min, respectively; p= 0.04572). The incidence of adverse effects was similar between groups. CONCLUSIONS: Enantiomeric bupivacaine (S75-R25) resulted in longer analgesia and less intense motor block as compared to racemic bupivacaine. PMID- 19475270 TI - [Comparative study between 0.5% bupivacaine, 0.5% enantiomeric mixture of bupivacaine (S75-R25) and 0.75% ropivacaine, all associated to fentanyl, for epidural cesarean section anesthesia.]. AB - BACKGROUND AND OBJECTIVES: Clinical trials with local anesthetic levo-enantiomers have shown higher safety due to lower cardiotoxicity. This study aimed at evaluating quality of anesthesia and maternal/fetal repercussions of 0.5% bupivacaine, enantiomeric 0.5% bupivacaine (S75-R25) and 0.75% ropivacaine, all associated to fentanyl, in epidural cesarean section anesthesia. METHODS: Participated in this study 90 full-term pregnant women, physical status ASA I, submitted to elective cesarean section under epidural anesthesia, who were divided into tree groups: group I - 23 ml racemic 0.5% bupivacaine with epinephrine; Group II -23 ml enantiomeric 0.5% bupivacaine (S75-R25) with epinephrine; Group III - 23 ml of 0.75% ropivacaine. Fentanyl (2 ml) was associated to local anesthetics in all groups. The following parameters were evaluated: onset, analgesia duration, sensory and motor block degree, time to hysterotomy and delivery, quality of muscle relaxation and anesthesia, maternal hemodynamic and respiratory changes, newborn vitality (evaluated through Apgar score and cord-blood gases analysis), and side-effects. RESULTS: There were no differences among groups, except for anesthesia quality. In groups with predominant levo-enantiomer fraction were clinically worse with the need for anesthetic complementation in three cases. Analgesia duration was longer in the ropivacaine group. CONCLUSIONS: Enantiomeric mixture 0.5% bupivacaine (S75-R25) and 0.75% ropivacaine for epidural anesthesia have provided as good conditions as racemic 0.5% bupivacaine for the surgical act. Newborn repercussions have shown that all solutions were equally safe. PMID- 19475271 TI - [Postoperative analgesia following orthopedic surgery: a study comparing perivascular lumbar plexus inguinal block with ropivacaine (3 in 1) and spinal anesthesia with morphine.]. AB - BACKGROUND AND OBJECTIVES: Perivascular Lumbar plexus inguinal block, (3-in-1 block) has been used for postoperative analgesia. This study aimed at comparing postoperative analgesia of 3-in-1 block and spinal morphine in patients submitted to lower limb orthopedic surgeries (LL). METHODS: Forty ASA I - II patients of both genders, aged 15 to 75 years, scheduled for LL orthopedic surgeries, were distributed in two groups: (M and LPB). Spinal anesthesia was performed in all patients at L3-L4 or L4-L5 with 20 mg of 0.5% isobaric bupivacaine. In group M (n = 20), 50 microg morphine were associated to local anesthetics. In group LPB (n = 20) 3-in-1 blockade was performed after surgery with 200 mg of 0.5% ropivacaine. Analgesia and pain intensity were evaluated at 4, 8, 12, 14, 16, 20 and 24 hours after surgery completion, in addition to spinal blockade level, surgery duration and complications. RESULTS: Analgesia duration in group LPB was 13.1 +/- 2.47 while all group M patients referred pain and lack of motor block in the first moment evaluated (4 hours). There has been blockade failure in one of the three nerves in three patients. The incidence of nausea and pruritus was significantly higher in group M. There was no significant difference between groups in urinary retention. There were no respiratory depression, arterial hypotension or bradycardia. Postoperative analgesia was more effective in group LPB as compared to group M at 4, 8, 12, 14 and 16 hours. There were no significant differences between groups at 20 and 24 hours. CONCLUSIONS: Postoperative analgesia induced by 3-in-1 blockade showed less side-effects as compared to spinal morphine with similar analgesia duration. PMID- 19475272 TI - [Dexmedetomidine/propofol association for plastic surgery sedation during local anesthesia.]. AB - BACKGROUND AND OBJECTIVES: Dexmedetomidine is a new alpha2-adrenergic receptor agonist with potentially useful characteristics for anesthesia. This comparative study aimed at evaluating the effects of dexmedetomidine on propofol requirements and cardiovascular/respiratory stability during plastic surgery sedation under local anesthesia. METHODS: Participated in this study 40 female patients aged 16 to 60 years, physical status ASA I or II, scheduled for elective face, nose and breast plastic surgeries under local anesthesia. Patients were randomly allocated into two groups of twenty patients: C (control) and D (dexmedetomidine). Sedation was achieved in both groups with 1 mg.kg-1 bolus propofol followed by continuous infusion at an adjusted rate to provide conscious sedation. Group D patients received continuous intravenous dexmedetomidine at a rate of 0.01 microg.kg-1.min 1, concomitant with propofol infusion. The following were evaluated: effect of dexmedetomidine on propofol requirements; cardiovascular (SBP, DBP, MBP, HR) and respiratory (SpO2, P ET CO2) parameters; quality of perioperative bleeding control and postanesthetic recovery features. RESULTS: Mean propofol infusion rate was lower in group D (35.2 +/- 5.3 microg.kg-1.min-1) as compared to group C (72.6 +/- 8.5 microg.kg-1.min-1). Mean SBP, DBP, MBP values have decreased as from 30 min in group D, remaining stable until procedure completion, while in Group C they have increased. HR remained stable in group D where as increased as from 30 min in group C. Mean time to open eyes under command was lower in group D (6.3 +/- 2.5 min) as compared to group C (8.9 +/- 2.7 min). Perioperative bleeding control was better in group D as compared to group C. CONCLUSIONS: Dexmedetomidine/propofol association for sedation is safe and has the following advantages: decrease in propofol requirements, cardiovascular stability, good perioperative bleeding control, lack of significant effects on ventilation. PMID- 19475273 TI - [Subdural anesthesia after epidural puncture: two case reports.]. AB - BACKGROUND AND OBJECTIVES: Epidural anesthesia is a widely used procedure nowadays. Accidental subdural anesthesia after epidural puncture is an uncommon complication. This report aimed at describing two cases of subdural injection which coincidentally have happened in consecutive anesthesias induced by the same anesthesiologist. CASE REPORTS: Case 1: Male patient, 41 years old, physical status ASA I, submitted to surgical ureteral calculi removal. Our choice was epidural anesthesia. Thirty minutes after beginning of induction, patient was communicative but sleepy with 100% SpO2, when he slowly began to show oxygen saturation decrease reaching 80% SpO2. Patient was unconscious with apnea and anisocoria. At this moment the diagnostic hypothesis was accidental subdural anesthesia. Patient was then intubated and maintained under mechanically controlled ventilation. After surgery, patient was referred to the recovery room and was discharged 6 hours after without any neurological complications. Case 2: Female patient, 82 years old, physical status ASA II, submitted to surgical proximal femur fracture fixation. Our choice in this case was continuous epidural anesthesia. Similar to the previous case, 30 minutes after she began to show SpO2 decrease, reaching 90%. Patient was uncons- cious with anisocoria, however without apnea. We decided to maintain the patient under constant surveillance and intubation was considered unnecessary. Our diagnostic hypothesis in this case was also accidental subdural anesthesia. At surgery completion patient was referred to the recovery room and was discharged 4 hours after without any neurological complication. CONCLUSIONS: Accidental subdural anesthesia is a very uncommon complication. The diagnostic hypothesis, in our cases, was limited to clinical data. There are several subdural blockade complications, but most of the times they are easily managed, provided they are promptly diagnosed and treated. PMID- 19475274 TI - [Desflurane: physicochemical properties, pharmacology and clinical use.]. AB - BACKGROUND AND OBJECTIVES: Following the development of nuclear chemistry with halogenate synthesis in the 50s of past century, several anesthetics were clinically studied and some of them had wide practical application. The search for the ideal agent continues. Currently, halothane, isoflurane, enflurane, sevoflurane and desflurane are in clinical use. All have advantages and disadvantages. Desflurane is the newest agent. This study aimed at describing physicochemical and pharmacological properties of desflurane and reporting clinical experiences with this agent. CONTENTS: Physicochemical properties and pharmacokinetic and pharmacodynamic properties of desflurane determine its clinical use. With a low boiling point, it volatizes easily in normal operating room temperatures and its high MAC requires it to be administered in high concentrations. So, the use of low fresh gas flow and special vaporizer is recommended for it to be economically feasible. In addition, the use of coadjuvant anesthetics, such as nitrous oxide, decreases its MAC and allows it to be used in lower concentrations. Its pharmacokinetics provides fast induction and recovery being also worth mentioning that it has a highly stable molecule and is minimally metabolized, thus being well tolerated by the human body. Its pharmacodynamic repercussions are dose-dependent and similar to other potent inhalation anesthetics. CONCLUSIONS: Desflurane is an additional step in the evolution toward the ideal anesthetic agent. Its physicochemical properties give it highly desirable pharmacokinetic characteristics which provide fast induction (progression) and recovery and also minimal metabolic degradation with the lowest organic toxicity among halogenate anesthetics, in addition to strong molecular stability, even in the presence of carbon dioxide absorbents. With special attention regarding vaporization, storage, and consumption, desflurane may be used even in large scale, being economically feasible. PMID- 19475275 TI - [Challenges in perioperative management of morbidly obese patients: how to prevent complications.]. AB - BACKGROUND AND OBJECTIVES: The incidence of morbid obesity has significantly increased in recent years, especially in developed countries. Excellent results of the surgical treatment of such condition have raised the interest in the anesthetic management of such patients. This study aimed at emphasizing critical issues for anesthesiologists dealing with morbidly obese patients. CONTENTS: Cardiovascular, respiratory, endocrine and metabolic changes have been frequently associated to obesity and may cause significant clinical repercussions in the perioperative period of such patients. Some practical anesthetic issues are discussed in this review. CONCLUSIONS: In addition to emphasizing most significant and frequent complications and their prevention, the importance of PEEP and adequate tidal volumes is also highlighted. PMID- 19475276 TI - [Diastolic dysfunction: its importance to anesthesiologists.]. AB - BACKGROUND AND OBJECTIVES: Until recently, heart failure was primarily viewed as an event affecting heart contractility. However recently, after the recognition that several patients with classic signs and symptoms of heart failure had normal systolic function, left ventricular diastolic function is receiving major attention. The increase in populations life expectancy, surgical and anesthetic techniques improvements of the high prevalence of risk factors are increasing the number of patients with diastolic failure or dysfunction being referred to surgery and anesthesia. This article aims at reviewing diastolic dysfunction definition, causes, prevalence, diagnosis, management and anesthetic implications. CONTENTS: Left ventricular diastolic function and its importance to anesthesiologists are described. CONCLUSIONS: There are no proven benefits of an anesthetic technique over the others. Primary anesthetic goals are to maintain normal volume status and sinusoidal rhythm, in addition to preventing tachycardia, arterial hypertension and ventricular ischemia. Beta-blockers are the drugs more frequently used to meet these goals. PMID- 19475277 TI - [Are we prepared to diagnose and managed malignant hyperthermia?]. AB - BACKGROUND AND OBJECTIVES: Malignant Hyperthermia (MH) is an uncommon but potentially lethal disease associated to halogenate agents and/or succinylcholine exposure. Resulting mortality and morbidity may be decreased by early diagnosis and specific treatment, including sodium dantrolene. Brazil has approximately 160 million inhabitants assisted by more than 6000 anesthesiologists. In the last decade, special attention was given to this disease, resulting in better informed anesthesiologists and more prepared hospitals to treat malignant hyperthermia (MH). This study aimed at measuring the level of information of Brazilian anesthesiologists regarding MH, in order to develop new approaches to control this disease. METHODS: A questionnaire with 20 questions on malignant hyperthermia diagnosis, prevention and treatment was mailed to the 6,164 members of the Brazilian Society of Anesthesiology. RESULTS: Questionnaires were returned by 646 anesthesiologists (10.4%). More than 90% of correct answers about clinical diagnosis and treatment were obtained. On the other hand, nearly 50% of anesthesiologists gave incorrect answers about muscle biopsy indication and clinical pharmacology of dantrolene. CONCLUSIONS: Results have indicated adequate knowledge about this topic, but has shown that some relevant issues need additional attention. The number of answers was significant to evaluate MH understanding of Brazilian anesthesiologists, but has also shown poor motivation. From these results it is possible to conclude that it is essential to intensify continuing education programs, contemplating all issues of this major anesthetic subject. PMID- 19475278 TI - [Could the understanding of racial differences prevent idiosyncratic anesthetic reactions?]. AB - BACKGROUND AND OBJECTIVES: There are several unanswered questions about the interethnic variability in anesthetic and adjuvant drugs responses. Current pharmacogenetic developments are taking us to the verge of being able to identify inherited racial differences which could predict individual patients anesthetic response. CONTENTS: The understanding of interethnic factors affecting drug response will allow anesthesiologists to prevent idiosyncratic reactions: (1) Caucasian: increased dopamine diuretic effect; prolonged apnea following succinylcholine or mivacurium; cardiac arrhythmias after halothane and catecholamines in Riley-Day syndrome; acute porphyria episodes after thiopental. (2) Afro-American: different therapeutic approaches, essential arterial hypertension caused by the poorert response to ACEI anti-hypertensives, AT1 blockers, beta-blockers and clonidine, contrasted with the best anti-hypertensive response of diuretics, calcium channel blockers, claverdilol; attenuated isoproterenol-mediated vasodilatation (beta2) and a better vasodilating response to sublingual nitroglycerine; lower t-PA-induced thrombolytic effect; slower recovery from intravenous anesthesia with propofol and remifentanil; less glycuronide conjugation of paracetamol and less pain relief by codeine in weak metabolizers (CYP2D6); melanin slows onset of epidermal analgesia with EMLA anesthetic cream; less epinephrine-induced mydriasis; major metacholine-induced bronchocospasm in asthmatic children; G-6-PD deficit in erythrocytes increases the risk for hemolysis to oxidative drugs in 10% of the Afro-American population. (3) Asians: toxic kinetic changes of meperidine and codeine; longer diazepam induced anxiolysis; postpartum intravenous ergonovine-induced coronary artery spasm; inter-relationships of GABA receptor, dehydrogenases and Japanese drinking behavior contribute to their higher sensitivity to alcohol. Cytochrome P450 isoenzymes show genetic polymorphisms in neuropsychotropic drugs metabolism and the slow acetylation of N-acetyltransferase in equatorial populations (95%) increases isoniazid and hydrazine toxicity. CONCLUSIONS: This review aimed at answering specific questions in the area of anesthetic idiosyncrasy related to the effect of ethnicity on drugs pharmacokinetics and pharmacodynamics, in addition to surgical patients safety by optimizing a more individualized neuropsychopharmacotherapy. PMID- 19475279 TI - [Ethics and animal experiments.]. AB - BACKGROUND AND OBJECTIVES: This is a major subject since the aim is to grant human beings physical, mental, social and spiritual well-being without forgetting the sacred rights of all animals. Most international codes dealing with health related research practices state that research developed in human beings should be based on previous lab animal experiments or on other scientific data. This article aimed at explaining ethics in animal experiments. CONTENTS: The concepts of dissertation and thesis, experimental thesis, experimental essay or pilot experiment and experimental animal facilities are reviewed. Then, a historical retrospective is drawn about the first attempt to develop experimental research policies during the mid 19th Century, in London. It is highlighted that some criteria defined by that time still persist. The first animal research ethical committee was created in Sweden in 1979, followed by the USA in1984. In Brazil, animal research ethical committees were created as late as in the 90s. The Federal Law 6638 was passed in May 1979 and provides for the didactic-scientific practice of animal vivisection. This law, however, is still waiting for regulation. In addition, there are some drafts being analyzed by the Congress, which provide for the use of animals for teaching and research purposes. Finally, the policies adopted by the Brazilian College of Animal Experiments and the Universal Declaration of Animal Rights are presented. CONCLUSIONS: Professors, postgraduates, residents and graduate students of a Medical School involved in animal research should be aware of the ethical principles aiming at protecting animals selected for scientific work. PMID- 19475280 TI - [Theoretical basis for the implementation of problem-oriented learning in anesthesiology residency programs.]. AB - BACKGROUND AND OBJECTIVES: Problem-oriented learning (POL) is a teaching method the primary objective of which is the accumulation of medical concepts in the context of clinical problems, and which has been widely used in medical graduation since the 60s. POL is based on the information processing theory where acquisition of new knowledge is made easier by activating preexisting knowledge about the subject, by the similarity between learning contexts and knowledge application and by information improvement. Other theories have been evoked to justify POL method in Medical teaching and in other areas. The POL method uses adult teaching concepts applied to medical learning episodes. CONTENTS: This article describes the POL method, its theoretical and psychological basis, the role of professors and students in the process and suggestions for its implementation. CONCLUSIONS: As compared to traditional methods, POL has as major advantages a higher level of students and professors satisfaction, a wider source of queries and search for knowledge and more time spent with individual learning. Since the method has no disadvantages as compared to traditional methods, it could be considered a valid alternative for teaching Anesthesiology in Medical Residency Programs. PMID- 19475281 TI - [Processed electroencephalogram in children anesthetized with sevoflurane. Is it feasible?]. AB - BACKGROUND AND OBJECTIVES: EEG-derived bispectral index (BIS), has been indicated as a major substrate for measuring hypnotic effects of anesthetic drugs. However, there are only limited data on the use of EEG in anesthetized children. This study aimed at evaluating changes in BIS, SEF95%, relative delta band frequency amplitude (d%) and suppression rate (SR) in children, correlating these changes with sevoflurane pharmacodynamic variables (EC and EC/MAC) as compared to adults. METHODS: Participated in this study 100 patients of both genders, aged 0 to 40 years, physical status ASA I and II. All patients were induced with sevoflurane followed by neuromuscular blocker at BIS 30. Patients were distributed in 5 groups: GI (20) - 0 to 6 months; GII (20) > 6 months to 2 years; GIII (20) > 2 to 12 years; GIV (20) > 12 to 18 years and GV (20) > 18 to 40 years. Five moments were evaluated for each group: M1 (awaken); M2 (BIS 60); M3 (BIS 50); M4 (BIS 40) and M5 (emergence). The following parameters were recorded for all moments: SBP, DBP, HR, BIS, SEF95%, d%, suppression rate, EC and EC/MAC. RESULTS: Both BIS and SEF95% values for all age groups directly correlated to sevofluranes EC/MAC at BIS values of 40, 50, 60 and at emergence, considering MAC values for age (p > 0.05). d% values in GI were higher than in any other group during all five moments (p < 0.05). CONCLUSIONS: Unlike d%, the variations of which seem brain maturation-related, BIS and SEF95% may be used to monitor sevofluranes anesthetic depth in children aged 0 to 12 years, observing the parameters suggested for adults. PMID- 19475282 TI - [Spinal anesthesia for cesarean section with 0.5% isobaric bupivacaine plus fentanyl and morphine: prospective study with different volumes]. AB - BACKGROUND AND OBJECTIVES: Spinal block for cesarean section was described few years after the first report of spinal anesthesia by Bier in 1899. It was not until the last 5 years that spinal anesthesia has become the most frequent anesthetic method for cesarean section at our hospital. This prospective study aimed at evaluating 0.5% spinal isobaric bupivacaine for cesarean section, injected after fentanyl and morphine, in the lateral position, and at correlating the incidence of hemodynamic changes and cephalad spread with different volumes. METHODS: Participated in this study 100 patients undergoing spinal anesthesia for elective cesarean delivery who were randomly allocated into three groups to receive: 4 ml (20 mg), 3 ml (15 mg) or 2.5 ml (12.5 mg) of 0.5% isobaric bupivacaine after 25 microg fentanyl plus 50 microg morphine. The following parameters were evaluated and compared: analgesia and motor block onset, cephalad spread of analgesia, cardiovascular changes and the incidence of nausea and vomiting. RESULTS: The three volumes of 0.5% isobaric bupivacaine produced comparable effects. Onset was longer for the lowest dose. There were no differences in cephalad spread, number of patients with high cervical levels, cardiovascular changes and post dural puncture headache. Maximum analgesic level was T4 (range: T3-T6) with 4 ml, T4 (range: T4-T11) with 3 ml and T4 (range: T4 T8) with 2.5 ml. No patient required ephedrine to treat arterial hypotension. Motor block was incomplete for all patients. One patient developed post dural puncture headache. CONCLUSIONS: Results of this study confirm that 0.5% isobaric bupivacaine, following fentanyl and morphine injected with separate syringes and in the lateral position, in doses of 2.5, 3 and 4 ml provides a fast and effective anesthesia for cesarean section. PMID- 19475283 TI - [Comparative study of 0.5% bupivacaine versus 0.5% bupivacaine enantiomeric mixture (S75-R25) in epidural anesthesia for orthopedic surgery]. AB - BACKGROUND AND OBJECTIVES: With the objective of finding a safer drug than racemic bupivacaine, several animal studies were performed with its enantiomers. This study aimed at evaluating the efficacy of 0.5% bupivacaine enantiomeric mixture (S75-R25) as compared to 0.5% bupivacaine in lumbar epidural anesthesia for lower limb orthopedic surgery. METHODS: Participated in this randomized double-blind study 38 adult patients, aged 17 to 69 years, physical status ASA I and II submitted to lower limb orthopedic surgery, who were distributed in two groups: Group B - 30 ml of 0.5% bupivacaine and Group BEM - 30 ml of 0.5% bupivacaine enantiomeric mixture (S75-R25). Sensory and motor block characteristics were investigated, in addition to the incidence of side effects. RESULTS: There have been significant weight differences in group BEM. Hemodynamic parameters were similar in both groups. There were no differences in time to reach Bromage score and peak block height. Also time to total motor block regression was similar between groups. There has been a significant difference in Bromage 2 score between groups, which was higher in group BEM. CONCLUSIONS: Adequate sensory and motor block for surgery was achieved in both groups with few side effects, suggesting that both solutions are safe in lumbar epidural anesthesia for orthopedic surgery. PMID- 19475284 TI - [Peripheral nerve stimulator for femoral nerve block. Is it really necessary?]. AB - BACKGROUND AND OBJECTIVES: There are several methods to locate the femoral nerve in the perivascular inguinal space, being the most common the use of a peripheral nerve stimulator. This study aimed at evaluating femoral nerve block performed with peripheral nerve stimulator as compared to the loss of resistance to air technique, both by single injection or with catheter insertion. METHODS: Sixty patients undergoing femoral nerve blocks were divided in four homogeneous groups (GA, GB, GC, GD). Thirty blocks were performed with single injection technique: 15 with disposable 21G needle (GA) and 15 with insulated needle adapted to the peripheral nerve stimulator (GC). The remaining 30 blocks were divided in 15 blocks performed with intravenous catheter (GB) and 15 with long Contiplex catheter (GD). All femoral nerve blocks were performed in the perivascular inguinal space. Perifemoral space was identified after the second loss of resistance to air (iliac fascia, GA and GC), and with 0.3 to 0.4 mA stimuli from peripheral nerve stimulator (GB and GD). The following parameters were evaluated: time to blockade performance, presence or absence of paresthesias or disesthesias, puncture difficulties and failures. RESULTS: There were no paresthesias or disesthesias. There have been two failures (p < 0.26) in the same GA patient, and two puncture difficulties due to recent and multiple blocks on the same site. There have been no significant efficacy differences between loss of resistance and peripheral nerve stimulator methods. Time for peripheral nerve stimulator block was longer (p < 0.001). CONCLUSIONS: Whereas the peripheral nerve stimulator is more widely used in the inguinal region, our study has shown that the loss of resistance to air technique is an effective and feasible alternative. PMID- 19475285 TI - [Comparative study of intercostal and interpleural block for post-cholecystectomy analgesia]. AB - BACKGROUND AND OBJECTIVES: Postoperative analgesia is a wish of all surgical patients and has been used by most anesthesiologists. In addition to opioids, local anesthetic agents have been employed for peripheral and central blocks. The purpose of this study was to evaluate and to compare intercostal and interpleural blocks for post-cholecystectomy analgesia. METHODS: Sixty patients undergoing open cholecystectomy with subcostal incision, received either intercostal block (Group IC, n = 30) or interpleural block (Group IP, n = 30), for postoperative analgesia, both with 0.5% bupivacaine (100 mg) with epinephrine. Analgesia duration and patients complaints were evaluated. RESULTS: Analgesia was considered satisfactory for both groups. Mean analgesia duration was 505 minutes for Group IP and 620 minutes for Group IC, with no statistical significant difference. Nausea, vomiting and mild abdominal pain were the most frequent postoperative complaints. There was no postoperative complication related to blockade and no pneumothorax was detected. CONCLUSIONS: We concluded that both techniques were effective in promoting post-cholecystectomy analgesia, but interpleural block was easier to perform. PMID- 19475286 TI - [Effects of spinal administration of large volumes of 2% lidocaine and 1% ropivacaine on spinal cord and meninges: experimental study in dogs]. AB - BACKGROUND AND OBJECTIVES: Spinal injection of large local anesthetic volumes after accidental dural puncture is an epidural anesthesia complication. This study aimed at investigating potential clinical and histological changes triggered by large volumes of 2% lidocaine or 1% ropivacaine in a simulated accidental spinal injection in dogs. METHODS: Twenty one dogs were randomly allocated into three experimental groups, which received spinal injections of: G1 - 0.9% sodium chloride, G2 - 2% lidocaine, G3 - 1% ropivacaine. Spinal puncture was performed in L6-L7 interspace. Anesthetic volume was 1 ml per 10 cm-distance between the occipital protuberance and the lumbosacral space (5 - 6.6 ml). After 72 hours of clinical observation animals were sacrificed and their spinal cords were removed for histological examination under light microscopy. RESULTS: No G1 animal presented clinical or histological changes in the spinal cord. There were two cases of nervous tissue necrosis in G2, however clinical changes were only observed in one of these dogs and in two other dogs which had no histological changes. There has been focal necrosis in the spinal cord nervous tissue of one G3 animal. All G3 animals remained clinically normal. CONCLUSIONS: Large volumes of 2% lidocaine have determined more intensive clinical and histological changes as compared to 1% ropivacaine. PMID- 19475287 TI - [Systolic pressure variation as an earlier hypovolemia indicator and a guide for volume replacement with hypertonic and hyperoncotic solution in dogs]. AB - BACKGROUND AND OBJECTIVES: Studies have introduced a new method for preload evaluation based on systolic pressure variation analysis (SPV) during mechanical ventilation. This research aimed at evaluating whether SPV and its delta down derived (ddown) are earlier hypovolemia indicators and guides for volume replacement with hypertonic and hyperoncotic solutions. METHODS: Twelve dogs were submitted to graded hemorrhage of 5% of their volume until reaching 20% of volume (14 ml.kg-1). Before (control) and after every hemorrhage, hemodynamic, ventilatory and blood parameters were evaluated. Then, dogs were submitted to volume replacement with 7.5% NaCl in 3.75% dextran 70 (SHD) (4 ml.kg-1), and the parameters were again evaluated 5 and 30 minutes after volume replacement. RESULTS: Mean blood pressure decreased during hemorrhage and increased after SHD infusion, however without returning to baseline values. Right atrium (RAP) and pulmonary artery pressure (PAP) decreased before and increased after volume replacement reaching values similar to baseline. Pulmonary capillary wedge pressure (PCWP) decreased after the first hemorrhage and remained below baseline values even after volume replacement. Cardiac index has not changed, but increased after SHD infusion reaching values above baseline. Stroke volume index (SVI) decreased before, and increased after volume replacement reaching values above baseline. Systemic vascular and pulmonary resistance did not change during hemorrhage, but decreased after volume replacement, with SVRI remaining below baseline values and SVPRI in levels similar to baseline. Left ventricular stroke work index (LVSWI) and right ventricular stroke work index (RVSWI) decreased before and increased after SHD infusion, with RVSWI remaining above baseline values and LVSWI in levels similar to baseline. SPV and ddown progressively increased during hemorrhage and decreased after volume replacement, however remaining above baseline values. Major SPV and ddown correlations were found with SVI, PWCP, RAP, PAP and LVSWI. CONCLUSIONS: In dogs under our experimental conditions, SPV and its derived ddown are early hypovolemia indicators and sensitive guides for volume replacement with hypertonic and hyperoncotic solutions. PMID- 19475288 TI - [Apnea in the postanesthetic recovery room: case report]. AB - BACKGROUND AND OBJECTIVES: Respiratory depression is a postoperative complication which may occur when opioids are employed in anesthesia. This report aimed at discussing a case of apnea in a conscious patient admitted to the post anesthetic recovery room, after thyroidectomy under general anesthesia with propofol, fentanyl and isoflurane. CASE REPORT: Female patient, 50 years old, 60 kg, physical status ASA I, submitted to thyroidectomy under general anesthesia induced with propofol (140 mg), fentanyl (350 microg) and atracurium (30 mg), and maintained with isoflurane, two subsequent atracurium boluses (10 mg each) and mechanically controlled ventilation. At surgery completion and after neuromuscular block recovery, patient was extubated, responded to breathing commands and cooperated during transfer to the stretcher, being taken to the PACU, where she arrived fully conscious. Minutes after, she was apneic, cyanotic and unresponsive. Manual ventilation was installed with 100% oxygen, followed by intravenous naloxone (0,2 mg) and patient recovered spontaneous breathing and consciousness. CONCLUSIONS: Respiratory care in the postoperative period, during transportation, PACU admission and stay should be continuous in patients receiving opioids, even when they seem fully conscious in leaving the operating room. PMID- 19475289 TI - [Anesthesia for septoplasty and turbinectomy in von Willebrand disease patient: case report]. AB - BACKGROUND AND OBJECTIVES: Although von Willebrands disease is the most common hereditary hemorrhagic disorder, there are few reports in Brazilian literature relating this disease to anesthesia. This report aimed at describing a case of general anesthesia for septoplasty and turbinectomy in a von Willebrands disease type I patient, prophylactically treated with desmopressin (1-deamine-8-D- arginine vasopressin, DDAVP) in the pre and postoperative period. CASE REPORT: A female patient, 19 years old, 58 kg, with hypothyroidism controlled with L tiroxine (75 mg) had her von Willebrands disease manifested three years before after a wisdom tooth extraction with persistent bleeding in the postoperative period. To prevent new per and postoperative hemorrhagic episodes, patient was prophylactically treated with desmopressin (0.3 microg.kg-1). Anesthesia was induced with midazolam (2.5 mg), fentanyl (150 microg), droperidol (2.5 mg), lidocaine (60 mg), atracurium (30 mg) and metoprolol (4 mg), followed by tracheal intubation and ventilation under intermittent positive pressure. Anesthesia was maintained with 2% sevoflurane in a mixture of 50% oxygen and nitrous oxide. This technique provided a good heart rate and blood pressure control during surgery. Patient remained with a nasal tampon for 24 hours and no bleeding was observed at its removal. Patient was discharged the day after surgery uneventfully. There were no immediate or late postoperative bleeding. CONCLUSIONS: The prophylactic treatment with DDAVP associated to the anesthetic technique used in this case was effective in controlling peri and postoperative bleeding. PMID- 19475290 TI - [Renal transplantation in Vater association patient: case report]. AB - BACKGROUND AND OBJECTIVES: Vater association is a polytopic disorder including several malformations of which radial hypoplasia is the most common observed at birth. This report aimed at describing a case of Vater association in a child submitted to renal transplantation. CASE REPORT: Male patient, 11 years old, 23 kg, Hbs positive, submitted to esophagostomy at 30 hours of life. Since 7 years of age patient is submitted to hemodialysis, currently via atrial catheter for the lack of other access ways. Renal transplantation with cadaver donor was performed without intercurrences with adequate diuresis after vascular anastomoses. Right iliac fossa hematoma was drained in the first postoperative day. Patient was discharged 21 days after transplantation with normal renal function. CONCLUSIONS: Vater association is an extremely rare and complex event and this report aimed at describing for the first time a renal transplantation with cadaver donor in a child with this congenital defect, the result of which has been fully satisfactory. PMID- 19475291 TI - [Anesthesia in Duchennes Muscular Dystrophy patient: case report]. AB - BACKGROUND AND OBJECTIVES: Duchennes Muscular Dystrophy is an X-linked recessive disorder, generally diagnosed in childhood, which progressively worsens to degenerate respiratory function. This report aimed at presenting the case of a patient with Duchennes Muscular Dystrophy diagnosed 2 years before, submitted to postectomy under general anesthesia with ketamine S. CASE REPORT: Male patient, 9 years old, with Duchennes Muscular Dystrophy diagnosed 2 years before, submitted to general anesthesia with intravenous levo-ketamine (1.5 mg.kg-1), under spontaneous ventilation manually assisted by Mapleson A Baraka system and penile block with 25 mg of 0.5% bupivacaine. Monitoring consisted of non invasive blood pressure, pulse oximetry, cardioscopy and esophageal temperature. There were no incidents during surgery, and after surgery patient had a few vomiting episodes, without other significant complications. Patient remained in hospital for 24 hours and was discharged asymptomatic. CONCLUSIONS: Very careful pre-anesthetic evaluation, adequate monitoring and drugs not predisposing to complications make surgery and postoperative period safe for Duchennes Muscular Dystrophy patients. PMID- 19475292 TI - [Patient with upper airway infectious disease. When to induce anesthesia?]. AB - BACKGROUND AND OBJECTIVES: Anesthesia in children with upper airway infection (UAI) is a major challenge for Anesthesiologists. This paper aimed at discussing why and when to induce anesthesia in UAI children. CONTENTS: Preoperative clinical history, factors contributing to peri and postoperative complications and the type of surgery and anesthetic technique favoring such complications are highlighted. CONCLUSIONS: The understanding of post-UAI respiratory tract changes, of the importance of accurately evaluating the severity of symptoms, of factors contributing to complications and of the best anesthetic technique will allow for the choice of patients at the lowest risk to develop perioperative complications. PMID- 19475293 TI - [Anesthesia in the afro-american population]. AB - BACKGROUND AND OBJECTIVES: A significant percentage of the 12 million Afro Americans may present physiological, pathophysiological and pharmacological changes able to impact the success of anesthesia; Brazilian Afro-American population (40%) is subject to those changes for having the same ethnic and geographic origin. This review aimed at re-evaluating racial differences bias on potential anesthetic drug and adjuvant effect changes during anesthesia. CONTENTS: The analysis of pathophysiological studies inherent to the historical migration of the African gene as compared to Caucasians shows significant racial differences between Afro-American and African populations, suggesting a close interface between genetics and environment able to affect anesthesia. Unfavorable Afro-American socio-economic conditions, as a result of 400 years of slavery, are still influencing the preservation of cultural and physiological differences beyond the color of the skin: organic system dysfunctions are related to CNS, CVS, respiratory and renal systems. However, different effects of anesthetic drugs and adjuvants, such as decreased local analgesic effect of the anesthetic ointment EMLA, increased propofol hypnotic effect and paracetamol toxicity, less anti-hypertensive effects of renin-decreasing drugs (ACEI, beta2 blockers and AT1), decreased beta2-vasodilator effects and less t-PA fibrinolysis, may affect pre and postanesthetic approaches, especially in hypertensive, renal, asthma or stroke Afro-American patients. CONCLUSIONS: Drug response may vary among different populations due to biological (age, gender, disease), genetic, cultural and environmental factors. Race should be taken into account during preanesthetic evaluation to prevent perioperative idiosyncratic reactions and assure the anesthetic-surgical success. PMID- 19475294 TI - [Hemodynamic and metabolic evaluation of dexmedetomidine and remifentanil continuous infusion in videolaparoscopic cholecystectomy: comparative study]. AB - BACKGROUND AND OBJECTIVES: Dexmedetomidine has been used for sedation and as coadjuvant drug in general anesthesia. This study aimed at evaluating cardiovascular and sympathetic-adrenal responses to tracheal intubation and pneumoperitoneum inflation with dexmedetomidine, as compared to remifentanil during anesthesia with sevoflurane for videolaparoscopic cholecystectomy. METHODS: Forty two physical status ASA I or II patients, aged 25 to 55 years, were randomly distributed in two groups: GI and GII. Anesthesia was induced with 1 microg.kg-1 dexmedetomidine (GI) or remifentanil (GII) continuous infusion for 10 minutes, followed by propofol and cisatracurium. Anesthesia was maintained with 0.7 microg.kg-1.h-1 dexmedetomidine or 0.5 microg.kg-1.h-1 remifentanil continuous infusion and different sevoflurane concentrations. SBP, DBP and HR were recorded in the following moments: M1 - before initial drug infusion; M2 - after end of initial drug infusion; M3 - after tracheal intubation; M4 - before pneumoperitoneum; M5 - after pneumoperitoneum; M6 - five minutes after pneumoperitoneum deflation; M7 - after tracheal extubation. Epinephrine and norepinephrine were dosed in M4, M5 and M6. Sevoflurane expired concentration (EC), EC/MAC ratio and sevoflurane consumption were recorded in M4, M5 and M6. RESULTS: SBP and DBP variations were higher in the dexmedetomidine group in M4 and M5. HR, epinephrine and norepinephrine levels were similar between groups. Sevoflurane EC was higher in M4 and M6 for GI, as well as EC/MAC ratio. There has been a higher sevoflurane consumption in GI, with a trend to less analgesics and anti-emetics consumption. CONCLUSIONS: In the conditions of our study, dexmedetomidine has inhibited catecholamine release during tracheal intubation and pneumoperitoneum, however, has not prevented blood pressure increase in response to peritoneal inflation. PMID- 19475295 TI - [Effects of low spinal morphine doses associated to intravenous and oral ketoprofen in patients submitted to cesarean sections]. AB - BACKGROUND AND OBJECTIVES: Low spinal morphine doses are effective in relieving postoperative pain of patients submitted to Cesarean sections, with low incidence of side-effects. This study aimed at evaluating postoperative analgesia and the incidence of side-effects in patients submitted to Cesarean sections under spinal anesthesia with hyperbaric bupivacaine and 0.05 mg and 0.1 mg morphine associated to intravenous and oral ketoprofen. METHODS: Sixty pregnant women, physical status ASA I and II, undergoing elective Cesarean sections, were divided in two groups: group 1 patients were given 0.1 mg spinal morphine, while group 2 received 0.05 mg morphine, both associated to 15 mg hyperbaric bupivacaine. All patients received perioperative 100 mg intravenous ketoprofen and oral ketoprofen at 8-hour intervals in the first postoperative day. Patients were assessed at 6, 12 and 24 hours after surgery for pain intensity and side-effects (sedation, pruritus, nausea and vomiting). Side-effects were also evaluated in the perioperative period. RESULTS: Both groups were similar in demographics and surgery and anesthesia duration. They were also homogeneous in postoperative pain intensity and presence of pruritus, sedation, nausea and vomiting. CONCLUSIONS: Spinal 0.05 mg and 0.1 mg morphine associated to intravenous and oral ketoprofen have provided the same postoperative analgesia and have determined the same incidence of side-effects. PMID- 19475296 TI - [Comparison between pressure controlled and controlled mandatory ventilation in the treatment of postoperative hypoxemia after myocardial revascularization]. AB - BACKGROUND AND OBJECTIVES: Pressure controlled ventilation (PCV) has been used as the ventilation mode of choice in coronary artery bypass graft surgery patients who develop severe hypoxemia in the immediate postoperative period. However, there are no evidences showing that pressure controlled ventilation is more effective in reversing postoperative hypoxemia than controlled mandatory ventilation (CMV). This study aimed at comparing the effects of both ventilation modes on systemic oxygenation in cardiac surgery patients who develop hypoxemia characterized by PaO2/FiO2 ratio lower than 200 in the immediate postoperative period. METHODS: Participated in this study 61 consecutive patients with PaO2/FiO2 ratio lower than 200 who were randomly allocated in two groups according to the ventilatory mode (CMV and PCV). Tidal volume, respiratory rate, inspiration/expiration ratio and positive end-expiratory pressure were kept constant throughout the study in both groups. PaO2/FiO2 ratio and pulmonary shunt were obtained 1 or 2 hours after ICU admission. RESULTS: A significant increase in PaO2/FiO2 ratio and a decrease in pulmonary shunt were observed in both groups one or two hours after mechanical ventilation. However, no differences were observed between both ventilatory modes. CONCLUSIONS: Both ventilatory modes were equally effective in reversing hypoxemia observed in the immediate cardiac surgery postoperative period. Results show that inspiratory flow patterns are not relevant in the treatment of post cardiac surgery hypoxemia. PMID- 19475297 TI - [Extraconal block for cataract extraction surgery with implantation of intraocular lens: influence of access way (upper or lower) in anesthetic outcome]. AB - BACKGROUND AND OBJECTIVES: There is no completely safe anesthetic technique for ophthalmic surgery. The introduction of extraconal anesthesia has increased the number of ophthalmic surgeries with blockade since the incidence of severe complications is lower, as reported by Hay in 1991. Extraconal blockades may be induced by several access ways, among them upper and lower ways. This study aimed at evaluating the influence access ways (upper or lower) in anesthetic outcome. METHODS: Participated in this study 164 patients of both genders, aged 23 to 92 years, physical status ASA I to IV, 1 and 2 Goldmans cardiac risk index, undergoing elective cataract extraction surgery with intraocular lens implantation. Patients were randomly distributed in two groups of 82 according to primary extraconal block access way: group UE (upper extraconal), group LE (lower extraconal). Blockade quality was evaluated by the following parameters: intraoperative pain, eyelid and/or eyeball movement, persistence of Bell s reflex, number of blocks needed for eye akinesia, and surgeons evaluation. RESULTS: Upper extraconal approach was associated to more effective eyelid (upper access - 56.1%; lower access 36.6%) and superior rectus muscle akinesia (upper access - 93.9%; lower access 65.9%) and also a lower incidence of supplementary blocks (upper access - 29.3%; lower access 42.7%). The lower extraconal approach was associated to more effective inferior rectus muscle akinesia (upper access - 72%; lower access - 84.1%), however without statistical differences. CONCLUSIONS: In the conditions of this study the upper extraconal approach was better as compared to the lower approach as the primary access way for anesthetic block for cataract extraction with intraocular lens implantation. PMID- 19475298 TI - [Intravenous clonidine in the induced arterial hypotension technique for tympanoplasty]. AB - BACKGROUND AND OBJECTIVES: Induced arterial hypotension is an effective technique to decrease surgical bleeding. Clonidine is an a2-agonist with central action which was proven to be safe in anesthesia. This study aimed at evaluating the efficacy of intravenous clonidine as the primary drug for induced arterial hypotension. METHODS: Participated in this prospective double-blind study 36 patients of both genders, physical status ASA I and II, who were randomly distributed in three groups of 12 patients receiving the following preanesthetic medication 15 minutes before anesthetic induction: 3 microg.kg-1 clonidine (C3), 5 microg.kg-1 clonidine (C5) or 0.9% saline solution (Control). Anesthesia was maintained with isoflurane in a maximum concentration of 2%. BP and HR were recorded before, 1 and 5 minutes after induction and at every 5 minutes of anesthesia. Patients receiving 2% isoflurane for more than 15 minutes and not presenting SBP below 80 mmHg were administered sodium nitroprusside to induce arterial hypotension. RESULTS: Sodium nitroprusside was needed in three C3 group patients (25%), one C5 group patient (8%) and eight control group patients (66%). Total nitroprusside dose to induce arterial hypotension in the control group was higher as compared to groups C3 and C5 (p < 0.01). The incidence of complications was similar among groups. CONCLUSIONS: Intravenous clonidine may lead to induced hypotension during tympanoplasties under balanced anesthesia with isoflurane concentration limited to 2%. In the conditions of this study, clonidine has not affected anesthetic quality and emergence time. PMID- 19475299 TI - [Effects of halothane, isoflurane and sevoflurane on cardiovascular responses to infrarenal aortic cross-clamping: experimental study in dogs]. AB - BACKGROUND AND OBJECTIVES: Infrarenal aortic cross-clamping is associated to cardiovascular effects. This study aimed at analyzing the effects of halothane, isoflurane and sevoflurane on cardiovascular function of dogs following infrarenal aortic cross-clamping. METHODS: Thirty mongrel dogs were randomly divided in three groups, according to equipotent (0.75 MAC) inhaled anesthetic doses: GH (n = 10) - 0.67% halothane; GI (n = 10) - 0.96% isoflurane; and GS (n = 10) - 1.8% sevoflurane. All dogs were submitted to infrarenal aortic cross clamping for 30 minutes. Hemodynamic parameters were measured at control (C), at 15 (Ao15) and 30 (Ao30) minutes of aortic cross-clamping, and immediately (DAo) and 15 (DAo15) minutes after aortic unclamping. RESULTS: In all groups, infrarenal aortic cross-clamping significantly increased mean blood pressure, right atrial pressure, cardiac index, stroke volume index, left ventricular work index and right ventricular work index. Pulmonary artery pressure significantly increased during cross-clamping in GI and GS groups while pulmonary capillary wedge pressure significantly increased in GH and GI groups. After aortic unclamping all hemodynamic parameters have returned to control levels with the exception of cardiac and stroke volume indices which remained high, followed by systemic vascular resistance index decrease. There have been no significant differences among groups in studied attributes, except for heart rate which was always lower in GH group as compared to other groups during and after infrarenal aortic cross-clamping. CONCLUSIONS: In dogs under our experimental conditions, equipotent concentrations (0.75 MAC) of inhalational halothane, isoflurane and sevoflurane have not attenuated cardiovascular responses to infrarenal aortic cross-clamping. PMID- 19475300 TI - [Autonomic hyperreflexia in tetraplegic pregnant patient: case report]. AB - BACKGROUND AND OBJECTIVES: Complications of pregnant patients with medullary injury include urinary infection, renal stones, anemia, decubitus ulcers, muscle spasms, sepsis, uterine hyperactivity and autonomic hyperreflexia. Autonomic hyperreflexia is the most severe anesthetic complication and should, before all, be prevented. It is often developed in patients with medullary transection at the level of the 5th to 7th thoracic vertebra or above. This report aims at presenting a case of tetraplegic pregnant patient with injury at the level of the 6th cervical vertebra, submitted to Cesarean section under continuous epidural anesthesia with 0.25% bupivacaine without vasoconstrictor associated to fentanyl. CASE REPORT: Caucasian, tetraplegic primiparous term patient, 39 weeks of gestational age, 22 years old, 63 kg, 168 cm, physical status ASA II, admitted for elective Cesarean section. Patient reported spinomedullary trauma at C6, three years ago. After previous hydration with 1500 ml saline, epidural anesthesia was induced with medial puncture at L3-L4 interspace with the patient in the lateral position, disposable 17G Tuohy needle and without previous local infiltration anesthesia. Immediately after needle insertion, there was adjacent paravertebral muscles contraction, blood pressure increase (BP = 158 x 72 mmHg) and heart rate increase (HR = 90 bpm). Patient, however, did not refer pain. Needle was removed and local anesthesia was induced. Epidural block proceeded with 20 ml of 0.25% bupivacaine without vasoconstrictor associated to 100 microg spinal fentanyl and epidural catheter insertion in the cephalad direction (3 to 4 cm). Surgery went on without intercurrences with no need for blockade complementation. There were two arterial hypotension episodes in the first 24 postoperative hours, which were treated with lactated Ringers solution. Epidural catheter was maintained for 48 hours. Patient was discharged three days after. CONCLUSIONS: For paraplegic or tetraplegic pregnant patients, continuous epidural anesthesia with low local anesthetic concentration without vasoconstrictor and associated to fentanyl is a good indication for instrumented or not vaginal delivery, and Cesarean sections to prevent autonomic hyperreflexia. It is also important that the epidural catheter remains for at least 24 hours after delivery to block sympathetic afference in case a crisis is triggered. PMID- 19475301 TI - [Left iliac artery injury during lumbar laminectomy: case report]. AB - BACKGROUND AND OBJECTIVES: Iliac artery injury during laminectomy is an uncommon, however very serious event. This report aimed at presenting a case of left iliac artery injury in patient submitted to lumbar laminectomy under spinal anesthesia, that was clinically manifested in the immediate postoperative period, seven hours after beginning of surgery. CASE REPORT: Male patient, physical status ASA I, 31 years old, 68 kg, submitted to lumbar laminectomy in prone position under spinal anesthesia in L2-L3 interspace with 20 mg 0.5% hyperbaric bupivacaine and 25 microg fentanyl. Surgery went on normally and seven hours after its beginning, already in the postoperative period, patient presented arterial hypotension, tachycardia, agitation and diffuse abdominal pain. An abdominal CT-scan showed extensive retroperitoneal hematoma and exploratory laparotomy revealed left iliac artery injury. After laparotomy, patient recovered without intercurrences. CONCLUSIONS: General anesthesia is mandatory depending on patients positioning and physical status. This case calls the attention to the fact that regardless of the anesthetic technique, there might be no operative field bleeding in the presence of vascular injury because this bleeding may be late. In our case, clinical manifestation was seven hours after beginning of surgery, when the patient had already recovered from anesthesia. However, the event (arterial hypotension) could have happened in the intraoperative period. PMID- 19475303 TI - [Evaluation criteria for 3-in-1 anesthetic block: Is the involvement of the obturator nerve common?]. AB - BACKGROUND AND OBJECTIVES: The participation of the obturator nerve in 3:1 blockades is controversial. Superficial surgical interventions in the medial face of the thigh strike femoral and obturator nerves dermatomes with imprecise, overlapped or even absent limits. The correlation between clinical outcome and other diagnostic methods may be conclusive about the involvement of the obturator nerve. CONTENTS: In general, regional block outcomes are confirmed more by the lack of dermatome sensitivity than by miotomes motor activity. As from the anatomic understanding of the pathway of plexus components of 3:1 blocks, clinical criteria aided by other diagnostic methods explain obturator nerve involvement. CONCLUSIONS: The symbiosis between 3:1 block outcome and different diagnostic methods is interpretative and conclusive and, according to literature indications about the obturator nerve participation, 3:1 block with single injection does not justify its name. PMID- 19475302 TI - [Latex allergy: accidental diagnosis after urological procedure. Case report]. AB - BACKGROUND AND OBJECTIVES: Allergy to natural rubber latex products has become a major source of concern, affecting both patients and healthcare workers. This report aimed at describing an accidental diagnosis of latex allergy after urological surgery under spinal anesthesia when patient presented clinical manifestations of anaphylactic shock. CASE REPORT: Male patient, 16 years old, with posterior urethra lesion who had been managed for the last 3 years with chronic indwelling latex urethral catheter due to two previous unsuccessful attempts to restore urinary drainage. During surgery under spinal anesthesia, patient presented soon after peritoneal cavity exploration, confusion, dyspnea, generalized pruritus and erythema, bronchospasm, arterial hypotension and tachycardia. Clinical manifestations faded gradually after treatment. During hospital stay and after blowing a toy balloon, patient developed contact hives on the face and bronchospasm, which were promptly treated. Prick and serologic test for latex-specific IgE have confirmed the diagnostic hypothesis of latex allergy. CONCLUSIONS: The combination of patients clinical history and lab findings have allowed for the identification of latex allergy. This entity is becoming highly relevant, especially for risk patients, as in this case report. PMID- 19475304 TI - [Maxillary nerve block for zygoma and orbital floor fractures reduction]. AB - BACKGROUND AND OBJECTIVES: There are few reports of zygomatic orbital floor or zygomatic arch fractures reduction under regional anesthesia. This study aimed at evaluating extraoral maxillary nerve block for zygoma and orbital floor fractures reduction. METHODS: Participated in this study 15 patients submitted to maxillary block according to Moores technique (lateral approach of the pterygoid plate) for reduction of isolated zygomatic arch fractures (8 patients) or orbit floor fractures associated to zygomatic arch fractures (7 patients). Patients were not premedicated. After sedation and local infiltration with 2 ml of 1.5% lidocaine and epinephrine 1:300,000 the maxillary nerve was blocked with 8 ml of the same anesthetic solution through a 10 cm 22G, short beveled needle. The following parameters were evaluated: blockade duration, onset, analgesia duration, failures, need for general anesthesia and complications. RESULTS: The first three blocks resulted in difficult punctures with two partial blocks and one failure. Remainder blocks were effective and patients have not referred any discomfort or pain during both blockade and surgery. Blockade time varied from 5 to 20 minutes while onset varied from 3 to 10 minutes. There were 7 vascular punctures (7 patients) however without hematomas. CONCLUSIONS: Zygomatic fractures reduction is feasible under maxillary nerve block when performed in pterygopalatine fossa inducing anesthesia in its two distal branches: zygomaticotemporal and zygomaticofacial nerves. PMID- 19475305 TI - [Postanesthetic routines of Brazilian anesthesiologists]. AB - BACKGROUND AND OBJECTIVES: There are no data on Postanesthetic Care Units (PACU) equipment, monitoring routines and discharge criteria adopted by Brazilian anesthesiologists. This study aimed at obtaining such data. METHODS: A nationwide survey was conducted with a random sample of 1123 anesthesiologists. Data were analyzed by simple and cross tabulation and logistic regression. RESULTS: Two hundred seventy-one questionnaires (26.59%) were analyzed. The study showed that most anesthesiologists work in institutions with PACUs equipped with resuscitation equipment, oxygen sources, aspirators, cardioscopes, pulse oximeters and with an anesthesiologist on duty. Neuromuscular function monitors and active heating devices are less frequent. In a descending order of frequency, the following parameters are routinely monitored: blood pressure, heart rate, SpO2, consciousness level, airway patency, respiratory rate, nausea and vomiting, postoperative pain and muscle strength. Oxygen therapy, anti-emetics and postanesthetic shivering control are prescribed on a routine or selective basis by most anesthesiologists who also record postoperative data. CONCLUSIONS: This study suggests that Brazilian anesthesiologists are concerned about patients safety during postanesthetic recovery, as shown by high equipment availability in the PACU and expressive routine monitoring ratios of isolated parameters. Some monitoring routines should be implemented to comply with new guidelines on postanesthetic care and new discharge criteria for outpatient procedures. PMID- 19475306 TI - [Xenon: pharmacology and clinical use]. AB - BACKGROUND AND OBJECTIVES: Xenon is a colorless, odorless, inert, non-irritating, non-pollutant, non-explosive, stable gas with low solubility coefficient and anesthetic properties. This review aimed at describing some pharmacological aspects and the clinical use of xenon in anesthesia. CONTENTS: Xenon is an extremely rare gas with MAC of 0.63 to 0.71, MAC-awaken of 0.32 +/- 5% and solubility coefficient of 0.14, providing fast, pleasant and well tolerated anesthetic induction, as well as 2 to 3 times faster recovery as compared to other agents. It has beneficial analgesic and minimal cardiovascular effects. Xenon may increase pulmonary resistance and produce the second gas effect, although not as important as N2O. It increases brain flow, intra-cranial pressure and cerebral perfusion pressure. Xenon is able to prevent adrenal gland stimulation. CONCLUSIONS: Xenon anesthetic properties grant it considerable advantages over other inhalational agents used in anesthesia. However, its high production costs make it prohibitive as compared to other existing techniques. New studies are being conducted with the aim of developing a more cost-effective method for using this gas. PMID- 19475307 TI - [Hemoglobin-based blood substitutes: current status and perspectives]. AB - BACKGROUND AND OBJECTIVES: Alternatives to red blood cells transfusion have been studied since the fifties. This study aimed at presenting current status and perspectives of hemoglobin-based blood substitutes. CONTENTS: Potential application areas are presented, in addition to clinical studies involving major hemoglobin molecules developed, their advantages and limitations. CONCLUSIONS: Several randomized trials have shown efficacy in avoiding or decreasing red blood cells transfusions, however there are some limitations and the future blood substitute shall at least have the same safety and efficacy of blood itself. PMID- 19475308 TI - Latex allergy. PMID- 19475309 TI - Effects of clonidine associated to hyperbaric bupivacaine during high-level spinal anesthesia. AB - BACKGROUND AND OBJECTIVES: Published data suggest that clonidine, an alpha2 adrenergic agonist, in association with bupivacaine, may increase the incidence of intraoperative hypotension and bradycardia during high-level spinal anesthesia. This study aimed at determining the synergistic potential of two clonidine doses (45 and 75 microg) and hyperbaric bupivacaine on characteristics and hemodynamic effects of high-level (T4) spinal anesthesia. METHODS: Participated in this randomized double-blind study, 60 ASA I patients scheduled for lower abdominal and limb surgery. Spinal anesthesia was induced with 17.5 mg (3.5 ml) of 0.5% hyperbaric bupivacaine plus the association of the following drugs: Control group (n = 20) - 0.5 ml isotonic saline solution; Clon 45 group (n = 20) - 45 microg (0.3 ml) clonidine + 0.2 ml isotonic saline solution; and Clon 75 (n = 20) - 75 microg (0.5 ml) clonidine. Surgery was only started when high level (T4) analgesia was consistently obtained. RESULTS: Sensory and motor block onset did not significantly differ among groups (p > 0.05). Both clonidine doses significantly prolonged analgesic block at T8 and motor block level 3 duration (determined by modified Bromage scale) (p < 0.05). Intraoperative arterial hypotension was observed only in Clon 75 group as compared to Control group (p < 0.05), while Clon 45 group had intermediate incidence between both groups. There was no significant difference among groups in bradycardia (p > 0.05). Both clonidine doses prolonged postoperative analgesia (time from spinal block to first postoperative analgesic request) (p < 0.05). CONCLUSIONS: High clonidine dose (75 microg) associated to hyperbaric bupivacaine during high-level spinal anesthesia (T4) induces a higher incidence of arterial hypotension but prolongs sensory block and postoperative analgesia similar to lower clonidine dose (45 microg) during upper spinal anesthesia. PMID- 19475310 TI - Spinal anesthesia for cesarean section: comparative study between isobaric and hyperbaric bupivacaine associated to morphine. AB - BACKGROUND AND OBJECTIVES: Bupivacaine preparations, plain or with glucose, are frequently used in the clinical practice. Blockade upper level is determined by local anesthetic spread in the CSF. This study aimed at comparing isobaric and hyperbaric bupivacaine in patients submitted to spinal anesthesia for Cesarean section. METHODS: In this prospective, randomized and double-blind study 60 patients submitted to spinal anesthesia for Cesarean section were distributed in two groups: IB - (0.5% isobaric bupivacaine, 12.5 mg) and HB - (0.5% hyperbaric bupivacaine, 12.5 mg). After monitoring, venous puncture was performed followed by hydration with lactated Ringers solution. Spinal puncture was paramedially performed at L3-L4 interspace with 27G Quincke needle. Following the CSF dripping, morphine (100 microg) and bupivacaine were separately injected at the speed of 1 ml. 15 s(-1). With the patient back to supine position, two parameters were recorded: onset time (absence of sensitivity in L3) at 1-minute intervals as well as motor and sensory block after 20 minutes. All patients were kept with preanesthetic blood pressure levels until umbilical cord clamping, and if necessary, ephedrine was administered. Neonates were evaluated by Apgars score at 1 and 5 minutes. Sensory and motor blocks were also evaluated at PACU 120 minutes after local anesthetic injection. RESULTS: Groups were homogeneous. Onset time: Group IB (1', 50") and HB (1', 33"), with no statistical difference. Motor and sensory block at twenty minutes showed no significant difference. Ephedrine consumption: IB (11.83 mg) and HB (14.17 mg), showed also no statistical difference. PACU motor block evaluation showed significant differences. CONCLUSIONS: We concluded that 12.5 mg isobaric and hyperbaric bupivacaine associated to morphine (100 microg) in spinal anesthesia for Cesarean section in term pregnant women are effective and present similar profiles. PMID- 19475311 TI - Low hypobaric bupivacaine doses for unilateral spinal anesthesia. AB - BACKGROUND AND OBJECTIVES: The possibility to achieve unilateral spinal anesthesia with 0.15% bupivacaine was studied with the purpose of minimizing hemodynamic changes, limiting the cephalad dispersion of the anesthetic and promoting a faster recovery. METHODS: Twenty ASA I - II patients undergoing orthopedic surgeries were given spinal 0.15% hypobaric bupivacaine through a 27G Quincke needle. Dural puncture was performed with patients in the lateral position, with the limb to be operated upwards, and 3.3 ml (5 mg) hypobaric bupivacaine were injected at the rate of 1 ml.15 s(-). Sensory and motor block (pinprick and 0 to 3 scale) were compared between operated and contralateral sides. RESULTS: Motor and sensory block in operated and contralateral sides were significantly different in all evaluated times. Unilateral spinal anesthesia was achieved in 75% of patients. All patients remained hemodynamically stable, and no one developed post-dural puncture headache. CONCLUSIONS: Hypobaric bupivacaine (5 mg) is able to provide a predominant unilateral block with the patient being kept twenty minutes in the lateral position. Major unilateral spinal anesthesia advantage is hemodynamic stability. PMID- 19475312 TI - Analgesia and sedation with epidural clonidine associated to 0.75% ropivacaine in the postoperative period of open cholecystectomy. AB - BACKGROUND AND OBJECTIVES: Epidural clonidine has analgesic properties and potentiates local anesthetic effects; there are, however, some side effects including: arterial hypotension, bradycardia and sedation. This study aimed at evaluating analgesia and sedation of clonidine associated to 0.75% ropivacaine in the postoperative period of open cholecystectomy. METHODS: Participated in this study 30 patients of both genders, aged 18 to 50 years, weighing 50 to 100 kg, physical status ASA I or II, submitted to cholecystectomy, who were distributed in two groups: Control Group (CG) received 0.75% ropivacaine (20 ml) with saline solution (1 ml); Experimental Group (EG) received 0.75% ropivacaine (20 ml) with clonidine (1 ml = 150 microg). Analgesia and sedation were observed at 2, 6 and 24 postoperative hours. RESULTS: Mean age was 41 yr in CG and 37 yr in EG. Mean weight was 67 kg in CG and 64 kg to EG. Postoperative sedation was significantly higher at 2 and 6 hours in the Experimental Group. Analgesia was observed in more EG patients as compared to Control Group. CONCLUSIONS: The association of clonidine and ropivacaine has produced longer analgesia and sedation at 2 and 6 hours of observation. PMID- 19475314 TI - Renal and cardiovascular effects of dopamine and 7.5% sodium chloride infusion: experimental study in dogs with water restriction. AB - BACKGROUND AND OBJECTIVES: Dopamine infusion for renal protection is controversial. This study aimed at observing the effects of dopamine, hypertonic solution and the association of both in dogs with water restriction, emulating preoperative fast. METHODS: The following renal function parameters were studied in 32 dogs anesthetized with sodium pentobarbital and fentanyl: effective renal plasma flow (sodium para-aminohippurate clearance), glomerular filtration rate (creatinine clearance), sodium, potassium and osmolar clearance, sodium and potassium fractional excretion and renal vascular resistance. Cardiovascular parameters were: mean blood pressure, heart rate, inferior vena cava pressure, cardiac index, hematocrit and peripheral vascular resistance index. Animals were randomly distributed in four experimental groups: Group 1 - G1 (n = 8) - control group; Group 2 - G2 (n = 8) - dopamine infusion (2 microg kg(-1) min(-1)); Group 3 - G3 (n = 8) - 7.5% sodium chloride (2 ml kg(-1)) and Group 4 - G4 (n = 8) - association of dopamine (2 microg kg(-1) min(-1)) and 7.5% sodium chloride (2 ml kg(-1)). Groups underwent four experimental stages lasting 30 minutes each, and involving moments M1, M2, M3 and M4. RESULTS: Dopamine group (G2) had mean blood pressure, renal vascular resistance and potassium excretion decrease. Hypertonic sodium chloride group (G3) had cardiac index, urinary volume, sodium and potassium clearance, sodium and potassium urinary excretion and sodium fractional excretion increase. Group receiving the association of hypertonic solution and dopamine (G4) had heart rate, cardiac index, effective renal plasma flow and sodium urinary excretion increase; there has also been systemic vascular resistance and plasma potassium index decrease. CONCLUSIONS: Our conclusion was that hypertonic sodium chloride solution was able to improve hemodynamic conditions and, as a consequence, renal function of dogs under 12-hour water restriction. The same was not true for 2 microg kg(-1) min(-1) dopamine which, in a similar situation, has not increased diuresis and sodium excretion. PMID- 19475313 TI - Extraconal block for cataract extraction surgery with implantation of intraocular lens: contribution of fentanyl associated to local anesthetics for quality of block and postoperative analgesia. AB - BACKGROUND AND OBJECTIVES: Loco-regional anesthesia for cataract extraction surgery offers as advantages minimum physiological changes, complete anesthesia, eye reflexes blockade, lower incidence of nausea and vomiting and shorter recovery time, in addition to postoperative analgesia. Continuous concern with blockade quality as well as with postoperative analgesia is responsibility of the anesthesiologist. This study aimed at evaluating whether fentanyl has contributed to blockade quality and postoperative analgesia in cataract extraction surgery with implantation of intraocular lens. METHODS: The association of fentanyl and 0.75% bupivacaine for eye blockade and postoperative analgesia was evaluated in 164 patients undergoing cataract extraction with implantation of intraocular lens (extracapsular technique). Patients were homogeneous in gender, demographics, operated eye, ASA physical status and Goldmans cardiac risk index. Patients were randomly allocated in two groups (82 patients each): with or without fentanyl. Blockade quality was evaluated according to the following parameters: intraoperative pain; eyelid and/or eyeball movement; Bells reflex persistence; number of blocks needed to produce akinesia and surgeons evaluation of blockade. Postoperative analgesia was evaluated by patients request for additional postoperative analgesia. RESULTS: Results have shown that fentanyl has significantly improved medial rectus muscle blockade quality (with fentanyl - 17.1%; without fentanyl - 32.9%) and has decreased postoperative analgesics consumption (analgesics with fentanyl - 20.7%; no analgesics with fentanyl - 41.5%). CONCLUSIONS: In the conditions of this study, fentanyl has improved block quality, has decreased medial rectus muscle motility and the need for postoperative analgesics. PMID- 19475315 TI - Effects of clonidine on cardiovascular responses to infrarenal aortic cross clamping. Experimental study in dogs. AB - BACKGROUND AND OBJECTIVES: Infrarenal aortic cross-clamping is associated to cardiovascular effects. Clonidine, an alpha2-agonist, determines bradycardia and hypotension. This study aimed at analyzing the effects of clonidine on the cardiovascular function of dogs submitted to infrarenal aortic cross-clamping. METHODS: This randomized study involved 16 mixed breed dogs randomly distributed in two groups: G Control - no clonidine; and G Clon - clonidine (5 microg kg(-1)) immediately before aortic cross-clamping, followed by 2 microg min(-1) m(2) until the end of the study. All dogs were submitted to infrarenal aortic cross-clamping during 45 minutes. Hemodynamic parameters were measured at control (C), 10 (Ao10) and 25 (Ao25) minutes after aortic cross-clamping, and 10 (DAo10) and 25 (DAo25) minutes after aortic unclamping. RESULTS: There were significant differences between groups in heart rate, mean blood pressure and cardiac index (G control > G Clon) during aortic cross-clamping. After aortic unclamping there were significant differences between groups in heart rate (G Control > G Clon), and right atrium and pulmonary capillary wedge pressures (G Clon > G Control). During aortic cross-clamping both groups have shown significant increase in right atrium pressure, pulmonary capillary wedge pressure, stroke volume index and left ventricular systolic work index, and significant decrease in pulmonary vascular resistance index. There has been significant increase in mean blood pressure, pulmonary artery pressure, cardiac index and right ventricular systolic work index in the G Control. The clonidine group has shown significant heart rate decrease. After aortic unclamping, both groups have shown significant heart rate and mean blood pressure decrease, while right atrium pressure and stroke volume index remained high. Right ventricular systolic work index remained high in the control group, while cardiac index values returned to close to baseline values. In the clonidine group, right atrium pressure, pulmonary wedge pressure and systolic index remained significantly high. CONCLUSIONS: In dogs under our experimental conditions, continuous intravenous clonidine has attenuated cardiovascular responses to infrarenal aortic cross-clamping. PMID- 19475316 TI - Hemorrhagic shock hemodynamic and metabolic behavior: experimental study in dogs. AB - BACKGROUND AND OBJECTIVES: Different experimental models have been used to illustrate hemodynamic and metabolic changes during hemorrhagic shock. This study aimed at observing hemodynamic and metabolic behaviors during a sequential and progressive model of hemorrhagic shock in dogs to determine which indices are earlier changed. METHODS: The study involved 13 dogs under total intravenous anesthesia with sodium pentobarbital, standard ventilation and previously splenectomized. Animals were not hydrated and bleeding velocity was dictated by animals blood pressure. Evaluated parameters were: hemodynamic (heart rate - HR, mean blood pressure - MBP, systemic vascular resistance index - SVRI, stroke index - SI, cardiac index - CI, shock index - i.Shock, left ventricular stroke work index - LVSWI, pulmonary capillary pressure - PCP, central venous pressure - CVP); and metabolic (mixed venous saturation - SvO2, venous oxygen pressure - PvO2, oxygen transport - O2T, oxygen consumption - VO2, oxygen extraction - TEO2, serum lactate). Results and parameters were evaluated in 6 different moments: M1 control, and the other moments corresponding to gradual 10% decrease in calculated volume for each animal. RESULTS: Hemorrhage has determined significant heart rate decrease in M6 only; MBP, CI, i.Shock, LVSWI decrease in all studied moments; mild CVP and PCP change in all moments; PVO2 and SVO2 decrease in all moments; O2T decrease, VO2 stabilization and TEO2 increase in all moments; shock index was increased from M1 to M3, was decreased in M4 and again increased until M6; SVRI was increased from M1 to M4, remained unchanged in M5 and has significantly decreased in M6; lactate has increased as from M5 and M6. CONCLUSIONS: Mean blood pressure, heart rate, central venous pressure and pulmonary capillary pressure have not reflected real volume status of dogs in our experimental model, oxygen transport, consumption and extraction rate are useful parameters to determine hemorrhagic shock reversibility and prognosis. PMID- 19475317 TI - Epidural blood patch in Jehovah's Witness: two cases report. AB - BACKGROUND AND OBJECTIVES: There are reports on epidural blood patch in Jehovah's Witness patients using a closed system which allows blood collection and epidural injection without loss of continuity. This report aimed at presenting two cases of Jehovah's Witness patients with post-dural puncture headache and treated with epidural blood patch in a closed venous blood transfusion system to the epidural space. Cases were reported by two different hospitals in two different cities. CASE REPORTS: One 21 years old male patient and one 32 years old female patient, with post-dural puncture headache after outpatient procedures. Since they were Jehovah's Witnesses, blood patch was performed with a closed system. System was prepared in sterile conditions using the following materials: two serum catheters cut in 60 cm segments, one two-way connection, one three-way tap and one 20 ml syringe. System was assembled to allow one connection to the puncture needle (20G), one connection to the three-way tap and the remaining two ways were connected to a 20 ml syringe and to the other serum catheter segment, which would be connected to the epidural needle. Lumbar region and right upper limb were disinfected with patients in the left lateral position. Epidural puncture was performed at L2-L3 interspace with 17G needle which was maintained fixed and connected to the serum catheter. Then, venous puncture was performed with a needle connected to the other edge of the serum catheter with the three-way tap directed from the vein to the syringe and 15 ml blood were aspirated. Redirecting the tap from the syringe to the epidural needle, the same 15 ml blood were re injected. CONCLUSIONS: In Jehovah's Witness patients refractory to clinical treatment, autologous blood injection may be performed through the above described technique after patients informed consent. PMID- 19475318 TI - Inhalational anesthetics analyzer as a method to detect anesthesia machine failures and prevent intraoperative awareness. Case report. AB - BACKGROUND AND OBJECTIVES: Although rare, intraoperative awareness is a severe general anesthesia complication. Anesthesia machine malfunction is one of several causes for anesthetic complications, among them intraoperative awareness. This report aimed at showing a case where the volatile anesthetic monitor has detected machine malfunction which could have led to intraoperative awareness. CASE REPORT: Female patient, 38 years old, 55 kg, physical status ASA I, with right breast cancer, admitted for radical mastectomy and immediate myocutaneous flap reconstruction. Epidural puncture was performed at T8-T9 with a 17-gauge Tuohy epidural needle followed by the introduction of 18-gauge epidural catheter and administration of 0.2% ropivacaine. General anesthesia was then induced, followed by sevoflurane vaporization. Although other monitoring parameters have not detected relevant findings, the inhalational anesthetic monitor has not identified the presence of sevoflurane, thus allowing the diagnostic of vaporizer leakage. CONCLUSIONS: Although rare, intraoperative awareness is a severe complication which should be prevented. Routine and thorough anesthesia equipment inspection before its use may minimize failures. The inhalational anesthetics monitor is useful whenever inhaled anesthetics are being used and may early detect anesthesia machine failures as in this case report. PMID- 19475319 TI - Incidence of cardiac surgery in octogenarian patients: retrospective study. AB - BACKGROUND AND OBJECTIVES: Increased life expectancy makes increasingly older patients to be submitted to cardiac surgeries. This study aimed at evaluating the incidence of octogenarian patients submitted to cardiac surgeries in the Heart Institute, Hospital das Clinicas, FMUSP, in the last 16 years. METHODS: The number of myocardial revascularization (MR) and valvar surgeries (VS) was analyzed for the period 1986 to 2001 and, within each group, the number of surgeries in octogenarian patients. Data were descriptively analyzed. RESULTS: Data have shown a progressive increase in the number of octogenarian patients submitted to cardiac surgeries. Myocardial revascularization surgeries have increased from 0.13% in 1986 to 3.5% in 2001. Valvar surgeries have increased from 0% in 1986 to 1.44% in 2001, with the highest rate of 3.02% in 1999. CONCLUSIONS: The understanding of pathophysiology and senility, and the advances in surgical trauma handling are allowing cardiac surgery resources to be expanded to elderly patients. Anesthetic technique should be carefully chosen, as well as hydration, ventilatory assistance and postoperative analgesia, to provide decreased morbidity and mortality in this higher surgical risk group. PMID- 19475320 TI - Anesthetic blocks to treat cancer pain. AB - BACKGROUND AND OBJECTIVES: Anesthesiologists have traditionally developed and mastered regional anesthetic techniques over the years. To help treating chronic pain, they need to transfer acquired know-how in addition to surgical indications, recommending procedures at the right time in a multidisciplinary approach. This research aimed at showing anesthesiologists that for anesthetic blocks to be useful and effective in treating chronic cancer pain, they have to be indicated in a timely manner, as part of a systemic approach where they need to play an active role. CONTENTS: WHO guidelines provide adequate pain control to most patients with advanced cancer disease. Its first three steps confirm the efficacy of this approach, with a low incidence of complications. There are however patients who experience undesirable side effects of systemic opioids, and the presence of bone metastases and neuropathies may determine noxious effects on those patients. Invasive techniques are seldom indicated, but they may provide analgesia in the treatment of opioid-resistant pain when adequately indicated. CONCLUSIONS: Neurolytic agent blocks, which require anesthesiologist skills, are the last treatment options when systemic drugs are unable to maintain desired effects or produce untreatable side effects. Anesthetic blocks and spinal opioids play an important role in the treatment of cancer pain and should be considered in specific situations as part of a multidisciplinary approach. PMID- 19475321 TI - Drug-delivery systems for local anesthetics: therapeutic applications. AB - BACKGROUND AND OBJECTIVES: Many researchers in the last four decades have been devoted to the development of drug-delivery systems. Since its first application in the pharmaceutical industry, many results have been obtained especially in the molecular manipulation of carriers and their interaction with encapsulated drugs. These new carriers have the advantage of bypassing encapsulated drugs restraining physicochemical properties (such as water or membrane solubility), thus improving pharmacodynamics (therapeutic effect potentiation), pharmacokinetics (control of tissue absorption and distribution) and toxic effects (lower local and systemic toxicity). Liposomes and cyclodextrins are among the most important carriers which have shown to be quite advantageous in the development of drug-delivery systems for local anesthetics. This study aimed at reviewing the interaction of local anesthetics with liposomes and cyclodextrins, the development of basic and applied research on the field, in addition to therapeutic applicability of these formulations. CONTENTS: Liposomes have the ability to control drug delivery to target tissues, fractionating drug release in its site of action. Cyclodextrins, on the other hand, change intensity and duration of effects due to low systemic drug absorption. Basic and clinical studies have pointed out that the administration of local anesthetics in liposome or cyclodextrin formulations induces slow release of the drugs, prolonging the anesthetic action and decreasing cardiac and nervous systems toxicity. CONCLUSIONS: Although studies are still in progress, drug-delivery systems are flagging a new direction for the development of safer and more effective local anesthetic formulations. PMID- 19475322 TI - Serum prevalence of hepatitis B virus in anesthesiologists. AB - BACKGROUND AND OBJECTIVES: Anesthesiologists are especially exposed to blood and secretions. Hepatitis B virus infection is the major occupational risk for health care professionals. This study aimed at evaluating the prevalence of Ag-HBs, anti HBs and anti-HBc among anesthesiologists of the city of Goiania, as well as their vaccination status. METHODS: Participated in this study 90 out of 200 anesthesiologists of the city of Goiania. Samples were collected by the author and consisted of 10 ml blood of a peripheral vein identified at collection. Blood was analyzed in the first 24 hours, under optimal conservation conditions. The following markers were detected by immunoenzymatic essay: anti-HBc, anti-HBs and Ag-HBs. Participants were personally contacted by the author and gave their written consent to participate in the study. Absolute secrecy of results and questionnaire information was assured. RESULTS: Analyzed material showed that 65 out of 90 (72.2%) were anti-HBs positive, as compared to 25 out of 90 (27.8%) who were negative. As to anti-HBc, 76 out of 10 (90.5%) were negative and 9 out of 90 (10%) were positive. No participant was Ag-HBs-positive. CONCLUSIONS: This study has shown 72.2% serum prevalence for anti-HBs. The prevalence of Hepatitis-B infection among anesthesiologists was 8.9%, represented by 8 anti-HBc +/anti-HBs +. Based on these results, vaccination campaigns and successful prevention should be intensified. PMID- 19475323 TI - Sedation and analgesia in intensive care. AB - BACKGROUND AND OBJECTIVES: Pain and anxiety may cause major discomfort, increase the risk for postoperative complications in surgical patients and may even prolong their hospital stay. This study aimed at reviewing concepts of sedation and analgesia in intensive care, updating knowledge and reviewing information available in the literature as well as already published consensus. CONTENTS: Sedation and analgesia are presented in separate, reviewing each group of available drugs, their major characteristics and side-effects. We have included some protocols used in our ICU for analgesia and sedation as well as the conclusions of the latest consensus of the American College of Critical Care Medicine and the Society of Critical Care Medicine. CONCLUSIONS: In spite of the therapeutic armamentarium available, there is a lack of understanding about major characteristics of drugs used for sedation and analgesia in Intensive Care. Developed consensus try to explain qualities and side-effects of most popular drugs, normalizing their use for ICU analgesia and sedation to benefit and faster recover patients. PMID- 19475325 TI - Don't prescribe tiotropium for smokers with an FEV1 above 60% predicted. PMID- 19475326 TI - Simulating distribution of trihalomethane in tap water in the area receiving a combination of advanced treated water and conventionally treated different source water: 1998, 1999 and 2002 data on Osaka Prefecture and its surrounding cities, Japan. AB - Empirical equations for explaining trihalomethane (THM) distribution were established based on data on tap water in Osaka City before and after starting the advanced treatment and were represented by the following equations for bromodichloromethane (S(1)), dibromochloromethane (S(2)) and bromoform distribution factors (S(3)) as a function of chloroform distribution factor (S(0)), respectively: S(1) = -0.97S(0)(2) + 0.75S(0) + 0.19 (regression coefficient: r = 0.71), S(2) = 0.13S (0) (2) -0.76S(0) + 0.51 (r = 0.98) and S(3) = 0.83S(0)(2) -0.99S(0) + 0.30 (r = 0.97). Further, the derived equations were verified by THMs data of Osaka Prefecture and its surrounding cities (except for Osaka City), receiving a combination of advanced treated water and conventionally treated different source water. PMID- 19475324 TI - The ADMIT series--issues in inhalation therapy. 2. Improving technique and clinical effectiveness. AB - Aerosol inhalation is considered the optimal route for administering the majority of drugs for the treatment of obstructive airways diseases. A number of Pressurised Metered-Dose and Dry Powder Inhalers are available for this purpose. However, inhalation of therapeutic aerosols is not without difficulty; it requires precise instructions on the inhalation manoeuvre, which is different from spontaneous normal breathing. Also, the characteristics of the inhaler device have to be suitable for the user. Available data indicate a frequent lack of knowledge demonstrated by health professionals and patients on the inhalation manoeuvre and handling of inhalers, resulting in a reduction of therapeutic benefit. This paper reviews the literature concerning the fundamental aspects of inhaler devices, inhalation manoeuvre and device selection, in an attempt to increase the knowledge of, and to optimise the clinical use of, therapeutic inhalers. PMID- 19475327 TI - Episodic trihalomethane species and levels in tap water at a start of operation of advanced treatment in Osaka Prefectural water supplies. AB - Dramatic changes in trihalomethanes of tap water caused by decreasing the chlorine dose from to break-point to zero at a pre-chlorination could be found during several years from starting the advanced treatment in Osaka Prefectural water utilities (from 1998 to 2002). In 1998 (break-point chlorination), chloroform was predominant (an average of 14.3 microg/L) and bromodichloromethane (5.96 microg/L), dibromochloromethane (4.19 microg/L) and bromoform (1.06 microg/L) were in the decreasing order. In contrast, in 1999 (chloramination), dibromochloromethane and bromodichloromethane were abundant trihalomethanes (6.61 and 5.72 microg/L) and followed by chloroform (4.14 microg/L) and bromoform (1.41 microg/L). Trihalomethane distribution in 2002 (non-chlorination) was almost the same as that in 1999. PMID- 19475328 TI - Genotoxic effects of nonylphenol and bisphenol A exposure in aquatic biomonitoring species: freshwater crustacean, Daphnia magna, and aquatic midge, Chironomus riparius. AB - The geno-, and eco-toxicity of nonlyphenol (NP) and bisphenol A (BPA) were investigated in Daphnia magna, and Chironomus riparius. BPA may exert a genotoxicity on both species, whereas NP-induced DNA damage occurred only in C. riparius. In NP-exposed D. magna, increased mortality, without effect on DNA integrity was observed, an example of a false-negative result from the biomarkers perspective. False-positive results from the genotoxicity were observed in BPA exposed D. magna and in NP-exposed C. riparius. Considering the importance of genotoxic biomarkers in ecotoxicity monitoring, DNA damage in these species could provide useful information. PMID- 19475329 TI - Mode of delivery after previous obstetric anal sphincter injuries (OASIS)--a reappraisal? AB - INTRODUCTION AND HYPOTHESIS: To prospectively evaluate anorectal symptoms, quality of life (QoL), sphincter integrity and function after subsequent childbirth following previous obstetric anal sphincter injuries (OASIS). METHODS: A validated Manchester Health Questionnaire, endoanal sonography and manometry were performed during the third trimester and 13 weeks postpartum. Women without objective compromise of anal function were recommended a vaginal delivery and the others a caesarean section. RESULTS: Seventy-three consecutive women with previous OASIS were seen during a subsequent pregnancy of whom 59 were reviewed 13 weeks following delivery. Anal manometry findings did not change significantly following a subsequent vaginal delivery or caesarean section. Only one new defect (internal sphincter) occurred after a vaginal delivery. There was no significant change in symptoms or QoL. Three (6.8%) sustained repeat OASIS. CONCLUSIONS: Women who have no antenatal evidence of objective compromise of anal sphincter function can be reassured that a vaginal delivery is not associated with any significant deterioration in function or QoL. PMID- 19475330 TI - Urogynecology triage clinic: a model of healthcare delivery. AB - INTRODUCTION AND HYPOTHESIS: To establish whether a nurse-led urogynecology triage clinic (UTC) is effective in terms of patient journey (from primary referral to first hospital contact until discharge), diagnosis, management, and outcomes. METHODS: The case notes of 300 patients attending the UTC in a university hospital between January 2006 and November 2007 were randomly selected for review. RESULTS: The mean interval from referral to first visit improved from 15.6 weeks (range = 12-32 weeks) to 4.6 weeks (range = 1-11 weeks, SD = 1.97) after UTC. Compared to pre-UTC, the mean period from first visit to final outcome improved from 11 months (range = 3.0-23.0 months) to 8.8 weeks (range = <1-60 weeks, SD = 11.15). Fifty-nine percent were discharged from the UTC without being seen by a specialist. CONCLUSIONS: By service redesigning, the UTC has reduced the number of clinic visits and patient journey time and has also shown that the majority of women with incontinence can be adequately managed by a specialist nurse. PMID- 19475331 TI - Techniques for performing laparoscopic liver resection in various hepatic locations. AB - Many studies have recently reported on laparoscopic liver resection, although its development has been slow compared to laparoscopy in other fields. The indications for the location of laparoscopic liver resection have previously been limited to easily accessible lesions. Performing laparoscopic liver resection in the posterior and superior parts of the liver has been considered difficult due to inadequate exposure, the poor operative field and the difficulty with parenchymal dissection. Flexible endoscopy, high definition imaging and various kinds of equipment for parenchymal transection have been introduced for clinical use. In addition, much experience with this procedure has been accumulated at many centers. Accordingly, there are an increasing number of reports on laparoscopic liver resection in difficult locations. At our institution, the location of the tumor is no longer a limitation to laparoscopic liver resection. However, for safer laparoscopic liver resection, the patient positioning and trocar placement should be individualized according to the tumor location. The type of resection also may depend on the remaining liver's functional capacity. We describe here the technical considerations for performing laparoscopic liver resection, including the technical considerations for performing laparoscopic liver resection for lesions located in the postero-superior segments of the liver. PMID- 19475333 TI - Lamivudine-to-entecavir switching treatment in type B chronic hepatitis patients without evidence of lamivudine resistance. AB - PURPOSE: A considerable number of chronic hepatitis B (CH-B) patients remain under continuous lamivudine treatment, although switching treatment to entecavir could be beneficial. We investigated the antiviral efficacy of switching treatment to entecavir in CH-B patients without apparent evidence of lamivudine resistance during the preceding lamivudine treatment. METHODS: Forty-four CH-B patients, who underwent lamivudine treatment for more than 6 months and showed no evidence of lamivudine resistance, switched to entecavir. Serial changes in hepatitis B virus (HBV) DNA were correlated with the patients' baseline HBV DNA at the commencement of entecavir administration. The entecavir-resistant substitution was examined by PCR-direct sequencing. The median follow-up period of entecavir treatment was 20 (10-23) months. RESULTS: All 31 patients with baseline HBV DNA <2.6 logcopies/ml maintained HBV DNA-negative status during entecavir treatment. Of seven patients having HBV DNA of 2.6-<4.0 logcopies/ml, all achieved undetectable HBV DNA at the end of follow-up. As for six patients having HBV DNA >or=4.0 logcopies/ml, three patients achieved undetectable HBV DNA, whereas virological breakthrough was observed in one patient at month 15. An entecavir-resistant virus having rtM204V, rtL180M and rtS202G substitutions was detected in this patient. CONCLUSIONS: The lamivudine-to-entecavir switching treatment may be generally recommendable in CH-B patients without evidence of lamivudine resistance during the preceding lamivudine treatment. However, great care should be taken with respect to the emergence of entecavir-resistance, especially in patients who do not respond well to the preceding lamivudine treatment. PMID- 19475334 TI - The oxidative stress status in diabetes mellitus and diabetic nephropathy. AB - The aim of this study is to assess the oxidative stress status in diabetes mellitus (DM) and diabetic nephropathy. The study group comprised 40 control subjects, 40 type 2 DM patients without complications and 37 diabetic nephropathies. Compared with control subjects, superoxide dismutase, glutathione peroxidase, catalase, vitamin C were decreased (P < 0.01). There was a significant increase in serum malondialdehyde (MDA), conjugated diene (CD), advanced oxidation protein products (AOPP), protein carbonyl (PC) and 8-hydroxy 2'-deoxyguanosine (8-OHdG) in diabetes patients when compared with normal subjects (P < 0.01). Moreover, these indexes were much higher in diabetic nephropathy than that of diabetic patients without vascular complications (P < 0.05, P < 0.01). There was a significant correlation between the serum glucose levels and PC, 8-OHdG (P < 0.05, P < 0.01). There were highly significant positive correlation of CD and MDA, AOPP and PC (P < 0.01). Plasma AOPP levels had a significant correlation with PC levels (P < 0.01). Our findings suggested that diabetes patients have more severe oxidative stress than normal persons and higher oxidative stress in diabetic nephropathy than those in patients without complications. Oxidative stress may play an important intermediary role in the pathogenesis of diabetes complications. PMID- 19475337 TI - Characterization of marine microalga, Scenedesmus sp. strain JPCC GA0024 toward biofuel production. AB - A marine microalga, strain JPCC GA0024 was selected as high amount of neutral lipid producers from marine microalgal culture collection toward biofuel production. The strain was tentatively identified as Scenedesmus rubescens by 18S rDNA analysis. The growth of strain JPCC GA0024 was influenced by artificial seawater concentrations. The optimum growth of 0.79 g/l was obtained at 100% artificial seawater. The lipid accumulation reached 73.0% of dry cell weight at 100% artificial seawater without additional nutrients for 11 days. Gas chromatography/mass spectrometry analysis indicates that lipid fraction mainly contained hydrocarbons including mainly hexadecane (C(16) H(34)) and 1-docosene (C(22) H(44)). Furthermore, calorimetric analysis revealed that the energy content of strain JPCC GA0024 was 6,160 kcal/kg (25.8 MJ/kg) of calorific value, which was equivalent to the coal engery. The strain JPCC GA0024, S. rubescens, will become a promising resource that can grow as a dominant species in the seawater for the production of both liquid and solid biofuels. PMID- 19475336 TI - Genetic analysis of heme oxygenase-1 (HO-1) in German Parkinson's disease patients. AB - Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons and the presence of intracytoplasmic inclusions (Lewy bodies). Iron, which is elevated in the substantia nigra (SN) of PD patients, seems to be of pivotal importance, because of its capacity to enhance the amplification of reactive oxygen species. Therefore, it is tempting that the iron-releasing key enzyme in heme catabolism, heme oxygenase-1 (HO-1), may represent a candidate for a genetic susceptibility to PD. In the current study, we examined a (GT)n fragment length polymorphism in the promoter region, as well as three coding SNPs in the HO-1 gene in order to assess if certain genotypes are associated with PD. Furthermore, peripheral blood expression levels of HO-1 in PD patients and healthy probands were compared. However, our analyses did not reveal a significant association of these genetic markers in the HO-1 gene with an increased susceptibility to PD. PMID- 19475335 TI - Neurotransmitters and prefrontal cortex-limbic system interactions: implications for plasticity and psychiatric disorders. AB - The prefrontal cortex (PFC) efferent projections to limbic areas facilitate a top down control on the execution of goal-directed behaviours. The PFC sends glutamatergic outputs to limbic areas such as the hippocampus and amygdala which in turn modulate the activity of the nucleus accumbens (NAc). Dopamine and acetylcholine neurons in the brainstem and basal forebrain/septal areas, which send outputs to NAc, hippocampus and amygdala, are also regulated by PFC glutamatergic projections, and seem to be of special relevance in modulating motor, emotional and mnemonic functions. Both the physiological and pathological changes in the PFC influence the activity of these limbic areas and the corresponding final-guided behaviours. We revise our most recent studies on PFC NAc interactions focussed on the role of dopamine and glutamate receptors in the PFC. Specifically, by performing microinjections/microdialysis studies we found that the activation of D2 dopamine receptors and the blockade of glutamate NMDA receptors in the PFC change the release of dopamine and acetylcholine in the NAc. We suggest the possibility that dopamine and glutamate receptors in the PFC could change the activity of dopamine and acetylcholine function in the hippocampus and amygdala. Finally, it is speculated that changes in the function of the PFC, associated with psychiatric disorders or due to environmental-dependent plasticity, can change PFC-limbic system interactions. PMID- 19475338 TI - The effect of composition on ion release from Ca-Sr-Na-Zn-Si glass bone grafts. AB - Controlled delivery of active ions from biomaterials has become critical in bone regeneration. Some silica-based materials, in particular bioactive glasses, have received much attention due to the ability of their dissolution products to promote cell proliferation, cell differentiation and activate gene expression. However, many of these materials offer little therapeutic potential for diseased tissue. Incorporating trace elements, such as zinc and strontium, known to have beneficial and therapeutic effects on bone may provide a more viable bone graft option for those suffering from metabolic bone diseases such as osteoporosis. Rational compositional design may also allow for controlled release of these active ions at desirable dose levels in order to enhance therapeutic efficacy. In this study, six differing compositions of calcium-strontium-sodium-zinc-silicate (Ca-Sr-Na-Zn-Si) glass bone grafts were immersed in pH 7.4 and pH 3 solutions to study the effect of glass composition on zinc and strontium release in a normal and extreme physiological environment. The zinc release levels over 30 days for all zinc-containing glasses in the pH 7.4 solution were 3.0-7.65 ppm. In the more acidic pH 3 environment, the zinc levels were higher (89-750 ppm) than those reported to be beneficial and may produce cytotoxic or negative effects on bone tissue. Strontium levels released from all examined glasses in both pH environments similarly fell within apparent beneficial ranges--7.5-3500 ppm. Glass compositions with identical SrO content but lower ZnO:Na(2)O ratios, showed higher levels of Sr(2+) release. Whereas, zinc release from zinc-containing glasses appeared related to ZnO compositional content. Sustainable strontium and zinc release was seen in the pH 7.4 environment up to day 7. These results indicate that the examined Ca-Sr-Na-Zn-Si glass compositions show good potential as therapeutic bone grafts, and that the graft composition can be tailored to allow therapeutic levels of ions to be released. PMID- 19475339 TI - Foam-like scaffolds for bone tissue engineering based on a novel couple of silicate-phosphate specular glasses: synthesis and properties. AB - Glass-ceramic scaffolds mimicking the structure of cancellous bone were produced via sponge replication technique by using a polyurethane foam as template and glass powder below 30 lm as inorganic phase. Specifically, a SiO2-based glass of complex composition and its corresponding P2O5-based "specular" glass were used as materials for scaffolding. The polymeric sponge was thermally removed and the glass powders were sintered to obtain a replica of the template structure. The scaffolds were investigated and compared from a structural, morphological and mechanical viewpoint by assessing their crystalline phases, volumetric shrinkage, pores content and interconnection, mechanical strength. In addition, the scaffolds were soaked in acellular simulated body fluid to investigate their in vitro behaviour. The produced scaffolds have a great potential for bone reconstructive surgery because their features, such as shape, strength, bioactivity and bioresorption, can be easily tailored according to the end use. PMID- 19475340 TI - Hyaline cartilage surface study with an environmental scanning electron microscope. An experimental study. AB - To obtain images of the articular surface of fresh osteochondral grafts using an environmental scanning electron microscope (ESEM). To evaluate and compare the main morphological aspects of the chondral surface of the fresh grafts. To develop a validated classification system on the basis of the images obtained via the ESEM. The study was based on osteochondral fragments from the internal condyle of the knee joint of New Zealand rabbits, corresponding to fresh chondral surface. One hundred images were obtained via the ESEM and these were classified by two observers according to a category system. The Kappa index and the corresponding confidence interval (CI) were calculated. Of the samples analysed, 62-72% had an even surface. Among the samples with an uneven surface 17-22% had a hillocky appearance and 12-16% a knobbly appearance. As regards splits, these were not observed in 92-95% of the surfaces; 4-7% showed superficial splits and only 1% deep splits. In 78-82% of cases no lacunae in the surface were observed, while 17-20% showed filled lacunae and only 1-2% presented empty lacunae. The study demonstrates that the ESEM is useful for obtaining and classifying images of osteochondral grafts. PMID- 19475341 TI - Total iron and heme iron content and their distribution in beef meat and viscera. AB - To determine the content of total iron (TFe) and heme iron (HeFe) in major cuts of meat and principal viscera of bovine origin. 55Fe (30 mCi) was injected into two 4-month-old calves. Triplicate samples of the 12 basic American cuts of meat and major viscera were obtained from each specimen. Samples were acid digested and their iron content was read by atomic absorption spectrophotometry. Duplicate samples of the basic cuts of meat and major viscera were analyzed to determine the concentration of 55Fe using a double isotopic technique. The mean and standard deviation of TFe for all cuts was 1.4 +/- 0.3 mg/100 g of meat. The mean TFe for organs was (per mg/100 g): 0.9 +/- 0.1 brain, 3.0 +/- 0.05 kidney, 3.2 +/ 0.04 heart, 5.7 +/- 0.2 lung, 6.0 +/- 0.1 liver, and 31.2 +/- 0.4 spleen. HeFe was 64% of TFe in meat and 72.8% in spleen, 53.8% in lung, 35.7% in brain, 35.0% in kidney, 27.3% in heart, and only 13.6% in liver. Blood contained 85.5% of the radioisotope and only 1.4% was found in muscle and 1.6% was found in viscera. Results suggest that bovine cuts of meat have a low variation in TFe and that HeFe comprises more than 60% of TFe. PMID- 19475342 TI - Clinical manifestations in trisomy 9. AB - Complete trisomy 9 is a lethal diagnosis and most fetuses diagnosed thus die prenatally or during the early postnatal period and majority of such cases have been known to end in spontaneous abortion in the first trimester itself. One such rare survival of fetus ending in normal delivery and surviving until 20 days is reported here detailing the clinical manifestations of the child during the period of survival. The salient clinical features observed were small face, wide fontanel, prominent occiput, micrognathia, low set ears, upslanting palpebral fissures, high arched palate, short sternum, overlapping fingers, limited hip abduction, rocker bottom feet, heart murmurs and also webbed neck, characteristic of this trisomy 9 syndrome. PMID- 19475343 TI - Recurrent Kawasaki disease. AB - We describe an infant who had recurrence of Kawasaki disease and responded to therapy with Intravenous Immune globulin (IVIG) and highlight the need for recognition of this vasculitis, which is being increasingly recognised in the Indian subcontinent. PMID- 19475344 TI - Acute pancreatitis as the initial presentation in pediatric systemic lupus erythematosus. AB - It is exceptionally rare for acute pancreatitis to be the presenting manifestation of childhood systemic lupus erythematosus. We report a 14-year-old girl who presented with a history of fever, generalized rash, arthralgia and abdominal pain. Her serum amylase was 1472U/L and lipase 3316 U/L suggestive of acute pancreatitis. Other investigations revealed pancytopenia, low complement, high 24-hour urinary protein and elevated ANA and dsDNA. She was treated with IV methylprednisone, followed by oral steroids. PMID- 19475345 TI - Deviated tongue: the presenting manifestation of spinal tuberculosis. PMID- 19475346 TI - Knowledge, attitude and practices among health care professionals regarding pain. AB - OBJECTIVE: To assess the knowledge, attitude and practices among health care professionals regarding pain in children. METHODS: This was a prospective descriptive survey conducted at a tertiary care hospital in north India. A semi structured questionnaire regarding pain in children was administered to pediatric residents and nurses in a teaching hospital. The questionnaire consisted of 24 items, of which 18 items were rated on a 5-point scale ('strongly agree' to 'strongly disagree') and 6 items were open-ended questions. RESULTS: The response rate was 89.5%. Of 77 participants, 47 (61.1%) were nurses and 30 (38.9%) were pediatric residents. The knowledge about pain scales among the studied healthcare professionals was not widespread. Majority of respondents believed that the best judge of intensity of pain is the child. Nearly two-thirds of the respondents felt that non-pharmacological measures were better to control pain and also their practices showed that most were willing to allow the parental presence during minor invasive procedures. CONCLUSION: There is need to improve the knowledge of health care personnel regarding pain assessment and management in children. PMID- 19475347 TI - Obesity and thyrotropinemia. AB - OBJECTIVE: To study the relation between body mass index (BMI) and TSH in euthyroid and subclinical hypothyroid obese children and compared serum TSH level among obese and overweight children. METHODS: Fifty consecutive children (aged 2 18 yr) presenting for obesity were studied. All cases with TSH > 10, low T3/T4, organic and syndromic obesity were excluded. Patients were divided into Group 1: Overweight (n=20) (BMI between 85(th) to 95(th) centile) and Group 2: Obesity (n=30) (BMI > 95(th) centile). Fisher's exact test, Mann-Whitney U test and Pearson's correlation were used for statistical analysis. P value < 0.05 was considered significant. RESULTS: Elevated TSH level (between 4.5-10 mIU/L) with normal T3, T4 was seen in 4/20 overweight and 9/30 of obese children (P=0.5219). The mean TSH was comparable in both the groups (3.22 +/- 3.1 mIU/L vs. 3.63 +/- 2.2 mIU/L, P=0.3491). Overall TSH showed no correlation with BMI (r= 0.0014, P=0.9924). CONCLUSION: The preliminary data did not show any relation between severity of obesity and TSH level. Further large scale data from population are required to confirm these findings. PMID- 19475348 TI - Impacted esophageal foreign body mistaken for chronic pharyngitis. PMID- 19475349 TI - High-frequency oscillatory ventilation for acute respiratory distress syndrome. AB - OBJECTIVE: To evaluate the effectiveness of HFOV in pediatric patients with acute respiratory distress syndrome. METHODS: In this retrospective study, we reviewed all 20 pediatric patients, who were consecutively ventilated with HFOV in the pediatric intensive care unit of a tertiary medical center, from January 2006 to February 2007. RESULTS: A total of 20 patients were enrolled. The median age of the subjects was 70 (3-168) months; 10 were male. All patients received conventional ventilation before HFOV. After initiation of HFOV, there was an immediate and sustained increase in PaO(2)/FiO(2) ratio. The PaO(2)/FiO(2) ratio was elevated and OI was decreased significantly after 10-20 minutes and maintained for at least 48 hours (p= 0.03, both). Thirteen of the 20 patients were successfully weaned. No significant change in the mean arterial pressure and heart rate was noted after HFOV. Overall survival rate was 65%. Of 20 patients, 11 patients suffered from extrapulmonary ARDS (ARDSexp) and 9 from pulmonary ARDS (ARDSp). When HFOV was initiated, there was significant increase in PaO(2)/FiO(2) and decrease in OI in ARDSexp compared to ARDSp (p= 0.03, both). Also mortality rate was significantly lower in patients with ARDSexp (9% vs.66%), (p= 0.01). CONCLUSION: In our study, HFOV was effective in oxygenation and seems to be safe for pediatric ARDS patients. HFOV affected ARDSp and ARDSexp paediatric patients differently. However prospective, randomized controlled trials are needed to identify its benefits over conventional modes of mechanical ventilation. PMID- 19475350 TI - Post-op systemic hypertensive crises in an infant with total anomalous pulmonary venous connection. AB - Systemic hypertension is not usually a complication following repair of total anomalous pulmonary venous connection (TAPVC). We report an infant with supracardiac TAPVC with hypertensive crises post-operatively resulting in pulmonary edema. We feel this might have been related to the pre-operative hemodynamics as described. Beta-blockers improved the hypertensive crises. PMID- 19475352 TI - Unusual presentations of Visceral leishmaniasis. AB - We report 3 cases of Visceral leishmaniasis, who presented with unusual clinical manifestations. One child was diagnosed as hemophagocytic syndrome; another masqueraded with features of leukemoid changes alongwith hemophagocytosis and trilineage myelodysplasia; the third case presented with pyothorax. All the three patients showed amastigote forms of Leishmania donovani and positive serology (rk39 antigen). They showed complete clinical, hematological and parasitological resolution with Amphotericin B therapy. PMID- 19475351 TI - Hypertension due to angiodysplasia. AB - Renovascular hypertension is non essential hypertension, wherein anatomically evident arterial occlusive disease and increased blood pressures are related as cause and effect. The hypertension is due to renal ischemia. Angiodysplasia is an uncommon angiopathy associated with heterogeneous histological changes that may affect the carotid circulation and the visceral and peripheral arteries. PMID- 19475353 TI - Anterior urethral valves and diverticulum. AB - Anterior urethral valves with associated urethral diverticulum is a rare but important cause of infravesical obstructive uropathy in children. This condition can be a cause of significant morbidity and can even lead to end-stage renal disease. This rare condition should be included in the differential diagnosis while evaluating male infants with infravesical obstructive uropathy. PMID- 19475354 TI - Oropharyngeal true teratoma. AB - Oropharyngeal teratoma in newborn is very rare. Here we report a case of oropharyngeal true teratoma where a 17-day-old female baby presented with a protruding mass from oropharynx with episodic respiratory distress and feeding difficulty complicated by aspiration pneumonia, and treated successfully with coordinated team approach. PMID- 19475355 TI - Fulminant candida infection in an infant with Acrodermatitis Enteropathica. AB - Acrodermatitis Enteropathica (AE) is an important nutritional disorder of children affecting both innate and cell mediated immunity. It predisposes to secondary bacterial and candida superinfections. We describe an infant with typical features of AE who had candida infection with a fulminant course. Need of early recognition and prompt initiation of therapy for fungal infection in AE is emphasized. PMID- 19475356 TI - Basal ganglia involvement in a child with herpes simplex encephalitis. AB - Herpes simplex encephalitis (HSE) is a leading cause of sporadic, nonepidemic viral encephalitis in children and adults. We report a very rare case of HSE with involvement of bilateral thalamus, putamen, upper pons and midbrain, with development of extrapyramidal symptoms which responded to corticosteroid therapy. A 15-mth-old female baby admitted with complaint of fever for 5 days and generalised tonic clonic seizure 10 hours before admission. On clinical examination patient was drowsy, temperature was 39.4 degrees C and vitals were stable with signs of increased intracranial tension. There were no signs of meningeal irritation. Patient gradually become unconscious in the next few hours and pupils were constricted bilaterally with development of atonia in all four limbs and neck muscles. Doll's eye phenomenon was absent. PMID- 19475358 TI - Sero-prevalence of viral co-infections in HIV infected children of Northern India. AB - OBJECTIVE: To assess the prevalence of viral co-infections in HIV infected children. METHODS: Children born to HIV seropositive parents and those children who were suspected to be HIV infected based on clinical presentation by the pediatrician were screened for HIV -1 and 2 antibodies as per National Aids Control Organization (NACO) guidelines. Those found to be seropositive for HIV infection were further tested for Hepatitis B&C, Herpes simplex virus and Human cytomegalovirus infection. RESULTS: Among 803 children screened, 101 were found positive for HIV antibodies. Among the five viral markers tested, HCMV IgG was positive in 88 children (87.1%). HCMV IgM was positive in 35 cases (34.6%). HBsAg tested positive in 30 children, while anti-HCV IgM was reactive in 27 cases. IgM anti- HSV antibodies were observed positive in 59 (58.4%) cases. Both hepatitis virus coinfection (HBsAg and anti- HCV IgM antibodies) was observed in 10 HIV positive children, while both Herpesviridae family viruses (HCMV -IgM antibodies and HSV -IgM antibodies) were positive in 30 cases (29.7%). CONCLUSION: Viral co infections are significantly higher in HIV positive children, which adds to significant mortality and morbidity and should therefore be screened in all HIV positive children for timely treatment in order to improve the quality of life and better survival of HIV infected children. PMID- 19475357 TI - Outcome of head trauma. AB - OBJECTIVE: To investigate the outcome of head trauma and its related factors in Iranian children. METHODS: In a nonrandomized cross-sectional study 380 patients younger than 18-yr-old admitted to the surgery ward of Ali-E-Bne-Abitaleb Hospital, Rafsanjan due to head trauma were included. In all of them, skull X-ray and brain CT scan were performed under the supervision of the neurologist and neurosurgeon according to special indications. Patients were followed till discharge from the hospital or death. At the time of discharge, the patients were evaluated by pediatrician. Demographic information and imaging findings were statistically analyzed using SPSS software. RESULTS: Male to female ratio was 3:1 Most cases were in the age range of 7-12 year. Seventy two percent and 11% of patients' admission was due to motor accidents and falling, respectively. Eighty two percent of patients were discharged with complete recovery; also 12% of skull radiographs and 17% of brain CT scans were abnormal. CONCLUSION: Head trauma had more prevalence and mortality in male than female. Also in the present study, motor accidents as an etiology of head trauma was more frequent than the western countries, which demands special precautions to decrease this problem. PMID- 19475359 TI - Cystic lymphangiomatous hamartoma masquerading as massive ascites. AB - We report a 4-year-old boy presenting with a tense massive ascites and large hydrocele. History and physical examination were unremarkable. Routine laboratory studies were normal. Abdominal ultrasonography revealed massive ascites. Contrast CT was suggestive of a large cyst covering the entire peritoneal cavity. At laparotomy, a large cystic tumor was found extending into the scrotum through the left inguinal ring. Histopathologic examination diagnosed the tumor as a cystic lymphangiomatous hemartoma. Although abdominal lymphangiomas are seen in children, but presenting as massive ascites with hydrocele is very rare. PMID- 19475360 TI - [Perianal ulcerations caused by potassium permanganate bath]. AB - A 73-year-old female patient presented with acute very painful perianal ulcerations. She reported using various ointments and later potassium permanganate baths because of maceration of the rima ani as a manifestation of her psoriasis vulgaris. Suddenly after starting the potassium permanganate baths, necrotic areas developed with then became ulcerated. After excluding the relevant differential diagnostic considerations, we diagnosed ulcerations caused by a caustic burn from potassium permanganate. After stooping potassium permanganate baths and employing modern moist wound therapy, we attained complete healing after 8 months of treatment. PMID- 19475361 TI - [Severe type 1-allergy to raw bell pepper]. AB - We report on a patient with rare anaphylaxis after ingestion of raw bell pepper. A complex cluster of sensitization including grass and birch pointed out a possible pollen-associated food allergy. We suggest that the severe reaction is due to cross-reactivity towards Bet v 1. Western blot showed binding of the patient's serum to an 11 kDa protein, which has not been described yet and might be a new allergenic structure of the bell pepper plant or a fragment of the Bet v 1-homologous bell pepper protein. PMID- 19475362 TI - [Sociomedical implications of the inability to commute in patients with cold urticaria]. AB - One of the important functions of the dermatologist working within a social medicine framework is the determination of social security disability benefits. The primary decision deals with the question which type of work the applicant can be asked to do and to what extent. Depending on the results of the medical assessment, social security disability benefits may be approved given that other insurance criteria specific to the applicant have been met. The following case demonstrates for the first time that a significant idiopathic cold urticaria leads to a severe constraint on keeping employment due to the inability to commute. The scenario shows that the cold urticaria severely restricts social and professional interactions and that the reduced ability to commute to the place of employment must receive special consideration within the context of a sociomedical evaluation. PMID- 19475363 TI - [Current treatment of focal hyperhidrosis. Surgical approaches]. AB - A variety of conservative and surgical therapy options are available for the treatment of focal hyperhidrosis. In case of severe therapy-resistant forms, surgery aims to achieve permanent reduction of sweating. For axillary hyperhidrosis, local surgical techniques are the method of choice with minimally invasive techniques favored in recent years. Sympathectomy is the ultima ratio for palmar hyperhidrosis; however, the procedure can lead to severe side effects. For most surgical techniques for hyperhidrosis, both long-term studies and side to-side comparisons are not available. PMID- 19475365 TI - Effects of exposure to heavy metals on viability, maturation, fertilization, and embryonic development of buffalo (Bubalus bubalis) oocytes in vitro. AB - The aim of the present study was to examine the effect of heavy metals, cadmium and lead, on buffalo oocyte viability and in vitro development. Oocytes were aspirated from ovaries of slaughtered buffaloes. Only viable and metabolically active oocytes with more than three layers of cumulus cell layers and homogeneous ooplasm were selected. Effects of nine concentrations (0, 0.005, 0.05, 0.5, 1.0, 1.5, 2.5, 5, and 10 microg/mL) of cadmium or lead on buffalo oocyte viability, morphological abnormities, maturation, and embryonic development in vitro were studied. Oocytes were cultured for 24 h and then checked for viability (0.05% trypan blue staining for 2 min), morphological abnormalities, and reduction assay by MTT test in experiment 1. The doses of cadmium and lead causing 100% oocyte death (1-day culture) were determined (experiment 2). In experiment 3, viable oocytes were matured in vitro in media containing different levels of cadmium or lead and then inseminated in vitro with frozen-thawed spermatozoa, and the resultant cleaved embryos were cultured in a control embryo culture medium for 8 days. In experiment 4, oocytes were cultured in control oocyte maturation medium, then fertilized, and the resultant embryos were cultured in media containing different levels of cadmium or lead for 8 days. The number of cells in the trophectoderm and inner cell mass (ICM) and the total cell counts (TCN) of blastocysts derived by in vitro culture of two- to four-cell-stage embryos (produced in control medium) in media containing 0, 0.005, 0.05, 0.5, and 1.0 microg/mL of cadmium or lead were analyzed by differential staining technique (experiment 5). Cadmium and lead were found to have a dose-dependent effect on viability, morphological abnormities, maturation, cleavage and morula/blastocyst yield, and blastocyst hatching. A significant decline in viability of oocytes was observed at 1.0 mg/mL cadmium or lead compared to the control group. The doses of cadmium and lead causing 100% oocyte death (1-day culture) were 18 and 32 microg/mL, respectively. Cadmium and lead at 1.0 and 2.5 microg/mL, respectively, caused a significant reduction of maturation of oocytes compared to the lower concentrations. No cleavage or morulae/blastocysts were produced when the oocytes/embryos were cultured in media containing 2.5 and 5.0 mg/mL of either cadmium or lead, respectively. Similarly, no morulae/blastocysts were produced from cleaved embryos cultured in media containing 2.5 and 5.0 microg/mL cadmium and lead, respectively. The developmental block, degeneration, and asynchronous divisions were higher in embryos exposed to cadmium than in those exposed to lead. TCN and number of cells in ICM were significantly lower in blastocysts derived from two- to four-cell-stage embryos cultured in media containing heavy metals. In conclusion, cadmium and lead lowered the viability and development of buffalo oocytes but at a concentration higher than that estimated in the body fluids and environment. Cadmium was found to be more ovotoxic than lead. PMID- 19475364 TI - The economic costs of diabetes: a population-based study in Tehran, Iran. AB - AIM/HYPOTHESIS: The aim of the study was to determine the annual healthcare expenditures of an individual with diabetes in Tehran, between March 2004 and March 2005. METHODS: This prevalence-based 'cost-of-illness' study was conducted in two phases. In the first phase, 23,707 randomly selected individuals were interviewed to gather a cohort of participants with diabetes. In the second phase, 710 diabetic patients and 904 age- and sex-matched controls were followed up for 1 year at intervals of 3 months and the direct (physician services, medications and devices, hospitalisation, laboratory, paraclinical and transport) and indirect (loss of productivity) expenditures were recorded. The excess costs of a person with diabetes were estimated through comparison with matched controls. The estimates were also extrapolated to the total population of Tehran and Iran. The costs were converted from the Iranian rial to the US dollar (exchange rate September 2004). RESULTS: Total annual direct costs of diabetic and control participants were $152.3 +/- 14.5 and $52.0 +/- 5.8, respectively, which is indicative of 2.92 times higher costs in diabetic patients. The most expensive components of direct costs were medications and devices, and hospitalisation in diabetic patients (28.7% and 28.6%, respectively). Total indirect costs were $39.6 +/- 2.4 and $16.7 +/- 1.1 in diabetic and non-diabetic individuals. The aggregate annual direct costs of diabetes were estimated to be $112.424 +/- 10.732 million and $590.676 +/- 65.985 million in Tehran and Iran, respectively. Diabetes complications contributed 53% of the aggregate excess direct costs of diabetes. CONCLUSIONS/INTERPRETATION: Diabetes is an expensive medical problem in Iran and planning of national programmes for its control and prevention is necessary. PMID- 19475366 TI - The impact of surveillance method and record source on autism prevalence: collaboration with Utah Maternal and Child Health programs. AB - With the increasing number of Utah children identified with autism spectrum disorders (ASDs), information on the prevalence and characteristics of these children could help Maternal Child Health (MCH) programs develop population building activities focused on prevention, screening, and education. The purpose of this study is to describe Utah's autism registry developed in collaboration with state MCH programs and assess the impact of different record-based surveillance methods on state ASD prevalence rates. The study was conducted using 212 ASD cases identified from a population of 26,217 eight year olds living in one of the three most populous counties in Utah (Davis, Salt Lake, and Utah) in 2002. ASD prevalence was determined using two records based approaches (administrative diagnoses versus abstraction and clinician review) by source of record ascertainment (education, health, and combined). ASD prevalence ranged from 7.5 per 1000 (95% CI 6.4-8.5) to 3.2 per 1000 (95% CI 2.5-3.9) varying significantly (P < .05) based on method and record source. The ratio of male-to female ranged from 4.7:1 to 6.4:1. No significant differences were found between the two case ascertainment methods on 18 of the 23 case characteristics including median household income, parental education, and mean age of diagnosis. Broad support is needed from both education and health sources as well as collaboration with MCH programs to address the growing health concerns, monitoring, and treatment needs of children and their families impacted by autism spectrum disorders. PMID- 19475367 TI - Investigation of a multimarker approach to the initial assessment of patients with acute chest pain. AB - Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article we summarize our previously published research, which assessed the value of myocyte injury, vascular inflammation, hemostatic, and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, we measured heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT proBNP, and peak cTnT were independent predictors of 1-year death/MI. Our research demonstrated that, in patients presenting within 4 hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification. PMID- 19475368 TI - Bacteriophage-based pathogen detection. AB - Considered the most abundant organism on Earth, at a population approaching 10(31), bacteriophage, or phage for short, mediate interactions with myriad bacterial hosts that has for decades been exploited in phage typing schemes for signature identification of clinical, food-borne, and water-borne pathogens. With over 5,000 phage being morphologically characterized and grouped as to susceptible host, there exists an enormous cache of bacterial-specific sensors that has more recently been incorporated into novel bio-recognition assays with heightened sensitivity, specificity, and speed. These assays take many forms, ranging from straightforward visualization of labeled phage as they attach to their specific bacterial hosts to reporter phage that genetically deposit trackable signals within their bacterial hosts to the detection of progeny phage or other uniquely identifiable elements released from infected host cells. A comprehensive review of these and other phage-based detection assays, as directed towards the detection and monitoring of bacterial pathogens, will be provided in this chapter. PMID- 19475369 TI - Electronic interfacing with living cells. AB - The direct interfacing of living cells with inorganic electronic materials, components or systems has led to the development of two broad categories of devices that can (1) transduce biochemical signals generated by biological components into electrical signals and (2) transduce electronically generated signals into biochemical signals. The first category of devices permits the monitoring of living cells, the second, enables control of cellular processes. This review will survey this exciting area with emphasis on the fundamental issues and obstacles faced by researchers. Devices and applications that use both prokaryotic (microbial) and eukaryotic (mammalian) cells will be covered. Individual devices described include microbial biofuel cells that produce electricity, bioelectrical reactors that enable electronic control of cellular metabolism, living cell biosensors for the detection of chemicals and devices that permit monitoring and control of mammalian physiology. PMID- 19475370 TI - Live cell optical sensing for high throughput applications. AB - Live cell optical sensing employs label-free optical biosensors to non-invasively measure stimulus-induced dynamic mass redistribution (DMR) in live cells within the sensing volume of the biosensor. The resultant DMR signal is an integrated cellular response, and reflects cell signaling mediated through the cellular target(s) with which the stimulus intervenes. This article describes the uses of live cell optical sensing for probing cell biology and ligand pharmacology, with an emphasis of resonant waveguide grating biosensor cellular assays for high throughput applications. PMID- 19475371 TI - Application of microbial bioreporters in environmental microbiology and bioremediation. AB - Bioreporters have been widely acknowledged to represent new and novel approaches in applied microbiology. Despite a plethora of constructions covering a diverse range of detection devices and host organisms, genuine applications are rare. Here, their application in the areas of general environmental microbiology, analytical detection and bioremediation are summarised and critically considered. Future applications require a more integrated approach such that those constructing bioreporters are aware of the needs of the end-user. A decade ago, predictions were made of the pivotal role of bioreporters and our future reliance; this fortune telling may take another decade to reach fruition. PMID- 19475372 TI - Surface functionalization for protein and cell patterning. AB - The interaction of biological systems with synthetic material surfaces is an important issue for many biological applications such as implanted devices, tissue engineering, cell-based sensors and assays, and more generally biologic studies performed ex vivo. To ensure reliable outcomes, the main challenge resides in the ability to design and develop surfaces or artificial micro environment that mimic 'natural environment' in interacting with biomolecules and cells without altering their function and phenotype. At this effect, microfabrication, surface chemistry and material science play a pivotal role in the design of advanced in-vitro systems for cell culture applications. In this chapter, we discuss and describe different techniques enabling the control of cell-surface interactions, including the description of some techniques for immobilization of ligands for controlling cell-surface interactions and some methodologies for the creation of well confined cell rich areas. PMID- 19475373 TI - Sensors in disposable bioreactors status and trends. AB - For better control of productivity and product quality, detailed monitoring of various parameters is required. Since disposable bioreactors become more and more important for biotechnological applications, adequate sensors for this type of reactor are necessary. The required properties of sensors used in disposable reactors differ from those of sensors for multiuse reactors. For example, sensors which are in direct contact with the medium must be inexpensive, but do not need a long life-time, since they can be used only once.This chapter gives an overview on the state of the art and future trends in the field of sensors suited for use in disposable bioreactors. The main focus here is on in situ sensors, which can be based on optical, semiconductor and ultrasonic technologies, but current concepts for disposable sampling units are also reviewed. PMID- 19475374 TI - Environmental applications of photoluminescence-based biosensors. AB - For monitoring and treatment of soil and water, environmental scientists and engineers require measurements of the concentration of chemical contaminants. Although laboratory-based methods relying on gas or liquid chromatography can yield very accurate measurements, they are also complex, time consuming, expensive, and require sample pretreatment. Furthermore, they are not readily adapted for in situ measurements.Sensors are devices that can provide continuous, in situ measurements, ideally without the addition of reagents. A biosensor incorporates a biological component coupled to a transducer, which translates the interaction between the analyte and the biocomponent into a signal that can be processed and reported. A wide range of transducers have been employed in biosensors, the most common of which are electrochemical and optical. In this contribution, we focus on photoluminescence-based biosensors of potential use in the applications described above.Following a review of photoluminescence and a discussion of the optoelectronic hardware part of these biosensor systems, we provide explanations and examples of optical biosensors for specific chemical groups: hydrocarbons and alcohols, halogenated organics, nitro-, phospho-, sulfo , and other substituted organics, and metals and other inorganics. We also describe approaches that have been taken to describe chemical mixtures as a whole (biological oxygen demand and toxicity) since most environmental samples contain mixtures of unknown (and changing) composition. Finally, we end with some thoughts on future research directions that are necessary to achieve the full potential of environmental biosensors. PMID- 19475375 TI - Disposable bioreactors for plant micropropagation and mass plant cell culture. AB - Different types of bioreactors are used at Nestle R&D Centre - Tours for mass propagation of selected plant varieties by somatic embryogenesis and for large scale culture of plants cells to produce metabolites or recombinant proteins. Recent studies have been directed to cut down the production costs of these two processes by developing disposable cell culture systems. Vegetative propagation of elite plant varieties is achieved through somatic embryogenesis in liquid medium. A pilot scale process has recently been set up for the industrial propagation of Coffea canephora (Robusta coffee). The current production capacity is 3.0 million embryos per year. The pre-germination of the embryos was previously conducted by temporary immersion in liquid medium in 10-L glass bioreactors. An improved process has been developed using a 10-L disposable bioreactor consisting of a bag containing a rigid plastic box ('Box-in-Bag' bioreactor), insuring, amongst other advantages, a higher light transmittance to the biomass due to its horizontal design. For large scale cell culture, two novel flexible plastic-based disposable bioreactors have been developed from 10 to 100 L working volumes, validated with several plant species ('Wave and Undertow' and 'Slug Bubble' bioreactors). The advantages and the limits of these new types of bioreactor are discussed, based mainly on our own experience on coffee somatic embryogenesis and mass cell culture of soya and tobacco. PMID- 19475376 TI - Secondary metabolites from higher fungi: discovery, bioactivity, and bioproduction. AB - Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin. PMID- 19475377 TI - Microbial transformation of nitriles to high-value acids or amides. AB - Biotransformation of nitriles mediated by nitrile-amide converting enzymes has attracted considerable attention and developed tremendously in the recent years in China since it offers a valuable alternative to traditional chemical reaction which requires harsh conditions. As a result, an upsurge of these promising enzymes (including nitrile hydratase, nitrilase and amidase) has been taking place. This review aims at describing these enzymes in detail. A variety of microorganisms harboring nitrile-amide converting activities have been isolated and identified in China, some of which have already applied with moderate success. Currently, a wide range of high-value compounds such as aliphatic, alicyclic, aromatic and heterocyclic amides and their corresponding acids were provided by these nitrile-amide degrading organisms. Simultaneously, with the increasing demand of chiral substances, the enantioselectivity of the nitrilase superfamily is widely investigated and exploited in China, especially the bioconversion of optically active alpha-substituted phenylacetamides, acids and 2,2-dimethylcyclopropanecarboxamide and 2,2-dimethylcyclopropanecarboxylic acid by means of the catalysts exhibiting excellent stereoselectivity. Besides their synthetic value, the nitrile-amide converting enzymes also play an important role in environmental protection. In this context, cloning of the genes and expression of these enzymes are presented. In the near future in China, an increasing number of novel nitrile-amide converting organisms will be screened and their potential in the synthesis of useful acids and amides will be further exploited. PMID- 19475378 TI - Recent developments in biodesulfurization of fossil fuels. AB - The emission of sulfur oxides can have adverse effects on the environment. Biodesulfurization of fossil fuels is attracting more and more attention because such a bioprocess is environmentally friendly. Some techniques of desulfurization have been used or studied to meet the stricter limitation on sulfur content in China. Recent advances have demonstrated the mechanism and developments for biodesulfurization of gasoline, diesel and crude oils by free cells or immobilized cells. Genetic technology was also used to improve sulfur removal efficiencies. In this review, we summarize recent progress mainly in China on petroleum biodesulfurization. PMID- 19475379 TI - Knock-in and knock-out: the use of reverse genetics in somatic cells to dissect mitotic pathways. AB - Reverse genetic methods, such as homologous gene targeting, have greatly contributed to our understanding of molecular pathways in mitosis, especially in yeast. The chicken B-lymphocyte line, DT40, represents a unique example among vertebrate somatic cells where homologous gene targeting occurs at very high frequency. DT40 cells therefore provide a useful and accessible somatic genetic system for wide-ranging biochemical and cell biological assays. In this chapter, we describe the main principles of homologous gene targeting, the concept of targeting construct design and the detailed experimental protocol of how to achieve successful knockouts. We also mention methods for conditional disruption of essential genes and conclude with specific procedures for the study of mitosis in DT40 cells. PMID- 19475380 TI - Functional dissection of mitotic regulators through gene targeting in human somatic cells. AB - With the human genome fully sequenced (1, 2), biologists continue to face the challenging task of evaluating the function of each of the approximately 25,000 genes contained within it. Gene targeting in human cells provides a powerful and unique experimental tool in this regard (3-8). Although somewhat more involved than RNAi or pharmacological approaches, somatic cell gene targeting is a precise technique that avoids both incomplete knockdown and off-target effects, but is still much quicker than analogous manipulations in the mouse. Moreover, immortal knockout cell lines provide excellent platforms for both complementation analysis and biochemical purification of multiprotein complexes in native form. Here we present a detailed gene-targeting protocol that was recently applied to the mitotic regulator Polo-like kinase 1 (Plk1) (9). PMID- 19475381 TI - RNAi in Drosophila S2 cells as a tool for studying cell cycle progression. AB - Genetic studies on model organisms, particularly yeasts and Drosophila melanogaster, have proven powerful in identifying the cell cycle machinery and its regulatory mechanisms. In more recent years RNAi has been used in a variety of genome-wide screens and single molecule studies to elucidate the mechanisms of cell cycle progression. In Drosophila cultured cells, RNAi is extremely simple, and a strong effect can be observed by adding the dsRNA to the cultured cells, with few complications of off-target effects. Functions in cell cycle progression can be followed by a variety of assays. One of the advantages of these cells is that they allow high-resolution spatiotemporal observations to be made by microscopy, with no particular complexity in terms of media and temperature. Here we discuss protocols for RNAi in Drosophila S2 culture cells, followed by the study of mitotic progression, through immunocytochemistry, live imaging, and flow cytometry analysis. PMID- 19475382 TI - Production of mitotic regulators using an autoselection system for protein expression in budding yeast. AB - A novel protein expression system in budding yeast is described which has been used to express many yeast mitotic regulators as well as a wide range of other recombinant proteins from several different species. The expression system relies on autoselection with essential genes to maintain high copy numbers of expression plasmids. Autoselection permits expression cells to be grown in rich medium with no need for plasmid selection with drugs or nutritional conditions. This optimizes growth and expression of recombinant proteins. The use of the expression system is illustrated by purifying budding yeast mitotic regulators, Cdc14 and Net1, and recapitulating their activities in vitro. PMID- 19475383 TI - Hydrodynamic analysis of human kinetochore complexes during mitosis. AB - Hydrodynamic analysis is a powerful tool to dissect the molecular architecture of macromolecular protein assemblies. These techniques have been successfully used in yeast systems but are also well suited to the analysis of protein complexes from human cells. Furthermore, the combination of hydrodynamic analysis with siRNA mediated protein depletion provides an excellent system to probe the composition of protein complexes isolated from human cells. In this chapter we describe the use of these approaches in the analysis of macromolecular protein complexes during mitosis in human cells, using the kinetochore as an example. PMID- 19475384 TI - Isolation of protein complexes involved in mitosis and cytokinesis from Drosophila cultured cells. AB - The identification of all the individual components that constitute the plethora of complexes in each cell type represents perhaps the most exciting challenge of postgenomic biology. This is particularly important in the study of events such as mitosis and cytokinesis, in which rapid and precise protein-protein interactions regulate both the direction and accuracy of these intricate processes. Here we describe an experimental strategy to isolate protein complexes involved in mitosis and cytokinesis in cultured Drosophila cells. This method involves the tagging of the bait protein with two IgG binding domains of Protein A and the isolation of the tagged bait along with its interacting partners by a single affinity purification step. These isolated complexes can then be analysed by several methods including mass spectrometry and Western blotting. Although this method has proven very successful in isolating mitotic and cytokinetic complexes, it can also be used to characterise protein complexes involved in many other cellular processes. PMID- 19475385 TI - Automated live microscopy to study mitotic gene function in fluorescent reporter cell lines. AB - Fluorescence live microscopy is a powerful technique to study complex cellular dynamics such as cell division. The availability of fluorescent markers based on GFP fusion proteins for virtually any cellular structure allows efficient visualization of specific processes, and the combination of different fluorophores can be used to study their coordination. In this chapter, we present methods for automated live cell microscopy to study mitotic gene function systematically and in high throughput. In particular, we provide protocols for efficient generation of fluorescent reporter cell lines stably expressing combinations of cellular markers, and provide detailed guidelines for optimizing imaging protocols for automated long-term live microscopy. PMID- 19475386 TI - Electron tomography of microtubule end-morphologies in C. elegans embryos. AB - In this chapter we describe the preparation of early mitotic C. elegans embryos for the tomographic reconstruction of end-morphologies of spindle microtubules. Early embryos are prepared by high-pressure freezing and freeze-substitution for thin-layer embedding in Epon/Araldite. We further describe data acquisition, tomographic reconstruction, and 3-D modeling of microtubules in serially sectioned mitotic spindles. The presented techniques are applicable to other model systems. PMID- 19475387 TI - Dissecting mitosis with laser microsurgery and RNAi in Drosophila cells. AB - Progress from our present understanding of the mechanisms behind mitosis has been compromised by the fact that model systems that were ideal for molecular and genetic studies (such as yeasts, C. elegans, or Drosophila) were not suitable for intracellular micromanipulation. Unfortunately, those systems that were appropriate for micromanipulation (such as newt lung cells, PtK1 cells, or insect spermatocytes) are not amenable for molecular studies. We believe that we can significantly broaden this scenario by developing high-resolution live cell microscopy tools in a system where micromanipulation studies could be combined with modern gene-interference techniques. Here we describe a series of methodologies for the functional dissection of mitosis by the use of simultaneous live cell microscopy and state-of-the-art laser microsurgery, combined with RNA interference (RNAi) in Drosophila cell lines stably expressing fluorescent markers. This technological synergism allows the specific targeting and manipulation of several structural components of the mitotic apparatus in different genetic backgrounds, at the highest spatial and temporal resolution. Finally, we demonstrate the successful adaptation of agar overlay flattening techniques to human HeLa cells and discuss the advantages of its use for laser micromanipulation and molecular studies of mitosis in mammals. PMID- 19475388 TI - Fluorescence imaging of the centrosome cycle in mammalian cells. AB - The formation of a bipolar spindle is essential for the equal segregation of duplicated DNA into two daughter cells during mitosis. Spindle bipolarity is largely dependent on the mitotic cell possessing two centrosomes that can each establish one spindle pole. The centrosome is also now known to regulate many other aspects of cell cycle progression, including G1/S progression, spindle orientation and symmetry, cytokinesis, and checkpoint signalling. As a result, defects in centrosome arrangement or number can lead to loss of cell polarity, defective cell division, and abnormal chromosome segregation, all events that are typical of cancer cells. Indeed, cancer cells often exhibit overduplicated centrosomes and multipolar spindles. Here, we outline a number of fluorescence imaging methodologies that can be used to study events of the centrosome duplication cycle, as well as the dynamics of individual centrosome proteins. Specifically, we discuss the generation and imaging of cell lines with fluorescently labelled centrosomes, the use of photobleaching methods to measure the dynamics of centrosome proteins, and assays for observing centrosome overduplication and centrosome separation in fixed and live cells. These experimental approaches can provide important information on the regulation of centrosomes, their role in normal cell cycle progression and how their deregulation might contribute to the deleterious phenotypes of malignant cancer cells. PMID- 19475389 TI - Visualization of fluorescence-tagged proteins in fission yeast: the analysis of mitotic spindle dynamics using GFP-tubulin under the native promoter. AB - Mitotic spindle microtubules pull chromosomes toward each pole to generate two daughter cells. Proper spindle formation and function are required to prevent tumorigenesis and cell death. The fission yeast Schizosaccharomyces pombe has been widely used as a model organism to understand the molecular mechanism of mitosis due to its convenience in genetics, molecular biology, and cell biology. The development of fluorescent protein systems and microscopy enables us to investigate the "true" behavior of proteins in living fission yeast cells using a strain with a fluorescence-tagged gene under its native promoter. In this way the level of expression of tagged protein is similar to the level of wild-type nontagged protein. In this chapter we illustrate standard methods to generate strains expressing fluorescently tagged proteins and to observe them under the microscope. Specifically, we introduce a GFP-tubulin strain to analyze the dynamic behavior of spindle microtubules. Observation of GFP-tubulin under its native promoter has illuminated the process of kinetochore-microtubule attachment process in fission yeast. PMID- 19475390 TI - Analysing kinetochore function in human cells: spindle checkpoint and chromosome congression. AB - During cell division microtubules of the mitotic spindle segregate the duplicated chromosomes into the two daughter cells. Chromosome-microtubule attachment is mediated by kinetochores, multiprotein complexes assembled on specialized regions of the DNA. Kinetochores modulate microtubule dynamics to generate the forces necessary to power chromosome movement and regulate the spindle checkpoint. Errors in kinetochore function can cause aneuploidy, a hallmark of 80% of solid tumors in humans, suggesting a fundamental link to tumorigenesis. Human kinetochores are complex protein machines with over 100 different proteins. Here we present fixed- and live-cell-based assays used to functionally categorize kinetochore proteins with regard to spindle checkpoint activity and kinetochore microtubule attachment. PMID- 19475391 TI - Probing kinetochore structure and function using Xenopus laevis frog egg extracts. AB - Kinetochores are multiprotein machines that initiate mitotic checkpoint signaling and control chromosome movement through interactions with microtubules. Our lab has utilized Xenopus laevis frog egg extracts to investigate the requirements for kinetochore assembly and disassembly in vertebrates. Egg extracts support the assembly of functional kinetochores that are capable of binding microtubules, aligning and segregating chromosomes, and sending spindle checkpoint signals. This is the only in vitro system that assembles functional kinetochores, making it particularly well suited for these types of studies. Probing kinetochore assembly using the biochemically tractable egg extract system has elucidated the intricate assembly requirements for numerous vertebrate kinetochore proteins. The following techniques have been used to characterize kinetochore assembly requirements. In addition, we describe assays that we utilized to identify factors that promote maintenance of preassembled kinetochores and those that induce kinetochore disassembly. PMID- 19475393 TI - The spindle checkpoint: assays for the analysis of spindle checkpoint arrest and recovery. AB - The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation by inhibiting anaphase onset until all chromosomes have established stable bipolar attachments. Here we describe a number of protocols that can be used to assay the ability of budding and fission yeast cells to (1) establish and maintain a spindle checkpoint arrest, and (2) segregate chromosomes efficiently upon recovery from mitotic arrest. We focus on experimental detail of the budding yeast protocols, but also point out important differences between budding and fission yeast assays. PMID- 19475392 TI - Live cell imaging of kinetochore capture by microtubules in budding yeast. AB - For high-fidelity chromosome segregation, kinetochores must be properly captured by spindle microtubules, but the mechanisms of initial kinetochore capture have remained elusive. Observation of individual kinetochore-microtubule interaction has been difficult, because multiple kinetochores are captured by microtubules during a short period and within a small space. By isolating one of the kinetochores from others through regulation of the activity of a centromere, we could visualize individual kinetochore-microtubule interactions in Saccharomyces cerevisiae. This technique, which we have called the 'centromere reactivation system', allowed us to dissect the process of kinetochore capture and transport on the mitotic spindle into several steps, thus enabling us to identify genes involved in each step. Kinetochores are captured by the side of microtubules extending from a spindle pole, and subsequently transported poleward along them. This process is evolutionarily conserved from yeast to vertebrate cells. Therefore, our system has proved useful in elucidating the underlying mechanisms of kinetochore capture by spindle microtubules. PMID- 19475394 TI - Measuring proteolysis in mitosis. AB - The targeted destruction of key regulators helps to drive the cell cycle. Here we describe a quantitative assay to measure destruction of different regulators in mitotic cells. This assay uses GFP-tagged substrates and time-lapse fluorescence microscopy of single cells to pinpoint the timing of destruction of different substrates at different stages in mitosis. PMID- 19475395 TI - An in vitro assay for Cdc20-dependent mitotic anaphase-promoting complex activity from budding yeast. AB - Cell cycle transitions are controlled, in part, by ubiquitin-dependent proteolysis. In mitosis, the metaphase to anaphase transition is governed by an E3 ubiquitin ligase called the cyclosome or Anaphase-Promoting Complex (APC), and a WD40-repeat protein co-factor called Cdc20. In vitro Cdc20-dependent APC (APC(Cdc20)) assays have been useful in the identification and validation of target substrates, and in the study of APC enzymology and regulation. Many aspects of the regulation of cell cycle progression have been discovered in the budding yeast Saccharomyces cerevisiae, and proteins purified from this model organism have been employed in a wide variety of in vitro assays. Here we outline a quantitative in vitro mitotic APC(Cdc20) assay that makes use of a highly active form of the APC that is purified from budding yeast cells arrested in mitosis. PMID- 19475396 TI - In vitro assays for the anaphase-promoting complex/cyclosome (APC/C) in Xenopus egg extracts. AB - The anaphase-promoting complex/cyclosome (APC/C), a large (20S) multisubunit E3 ligase, has an essential role to ubiquitylate numerous substrates at specific times during mitosis and G1 phase as well as in meiosis. The deregulation of the APC/C causes cell death or genomic instability, which is a hallmark of cancers. Although 13 years have passed since its discovery, the molecular mechanisms of the APC/C-dependent ubiquitylation and proteolysis are still poorly understood. The development of in vitro systems enables the identification of new substrates and investigation of the molecular mechanisms by which the APC/C recognizes its substrates. This chapter describes in vitro assays reconstituted in Xenopus egg extracts. PMID- 19475397 TI - Preparation of synchronized human cell extracts to study ubiquitination and degradation. AB - Ubiquitination and protein degradation regulate cell cycle progression in all eukaryotes. During mitosis, ubiquitination by the Anaphase-Promoting Complex/Cyclosome (APC/C) triggers sister chromatid separation and mitotic exit. The APC/C is tightly regulated by phosphorylation, ubiquitination, association of activators or inhibitors, and competitive binding of substrates. Much of our understanding of the mechanism of APC/C-dependent ubiquitination has been obtained from studies using extracts of Xenopus laevis eggs or synchronized human tissue culture cells. Here, we describe protocols to prepare extracts of synchronized human cells, and discuss experiments to use extracts for the biochemical analysis of APC/C-dependent ubiquitination. PMID- 19475398 TI - Biochemical analysis of the Anaphase Promoting Complex: activities of E2 enzymes and substrate competitive (pseudosubstrate) inhibitors. AB - The Anaphase Promoting Complex (APC) ubiquitin ligase is critical for multiple processes including cell cycle, development, meiosis, and senescence. The importance of regulation of the APC by substrate competitive (pseudosubstrate) inhibitors, such as Emi1 and BubR1, has recently been demonstrated. Substrate competitive inhibitors typically bind to enzymes via the same site as substrates, but by having any combination of increased enzyme affinity and low turnover numbers, are able to "clog" the ability of the enzyme to bind and turnover substrates. For the APC, these pseudosubstrates can both position and block the APC and have been well validated as critical regulators for the APC enzymes.We have found that the substrate competitive mechanism of inhibition is sensitive to the E2 activity driving APC catalyzed ubiquitination events. This chapter provides detailed protocols for multiple in vitro ubiquitination assays of increasing complexity and the use of pseudosubstrate inhibitors in these assays. These assays are instrumental in examining the use of E2 enzymes by the APC and the intimate relationship this has with pseudosubstrate inhibition. PMID- 19475399 TI - Suppression of acrylamide toxicity by carboxyfullerene in human neuroblastoma cells in vitro. AB - In our previous study, we found that caspase-dependent apoptosis played a role in the genesis of toxicity of acrylamide in human neuroblastoma (SH-SY5Y) cells (Sumizawa and Igisu in Arch Toxicol 81:279-282, 2007). In the present experiment, we examined whether carboxyfullerene may suppress the cytotoxicity of acrylamide because carboxyfullerene has been reported to protect nerve cells from various pathologic processes including apoptosis. Carboxyfullerene lowered lactate dehydrogense leakage and elevated cell viability in SH-SY5Y cells exposed to acrylamide. It also lowered caspase-3 activities and cell population in the sub G(1) phase induced by acrylamide. Nevertheless, carboxyfullerene enhanced cellular uptake of [(14)C]acrylamide. On the other hand, acrylamide markedly decreased glutathione (GSH)-content in cells and carboxyfullerene blocked the decrease. The toxicity of acrylamide was suppressed by adding GSH or GSH monoethyl ester, whereas it was not lowered by carboxyfullerene when GSH synthesis was inhibited by L: -buthionine-(S,R)-sulfoximine. Thus, the cytotoxicity of acrylamide including apoptotic processes is closely related to GSH level in SH-SY5Y cells and carboxyfullerene suppresses the toxicity by maintaining GSH content. Neither tricarboxylic acids without fullerene moiety nor hydroxylated fullerene showed comparable effects of carboxyfullerene (60 microM) against 1-5 mM acrylamide, suggesting the importance of the three malonic acid groups at specific positions in a fullerene molecule for the effects. PMID- 19475400 TI - Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose. AB - RATIONALE: The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. OBJECTIVE: The objective of the study was to use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. METHODS: Rats were trained for NSA during daily 23-h sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. RESULTS: Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23-h sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. CONCLUSIONS: These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID- 19475402 TI - The effect of heat treatment on the detection of peanut allergens as determined by ELISA and real-time PCR. AB - Peanut allergic reactions can result from the ingestion of even very small quantities of peanut and represent a severe threat to the health of sensitised individuals. The detection of peanut traces in food products is therefore of prime importance. Peanut traces which can be (unintentionally) present in food products have usually undergone one or more processing steps like roasting and baking. Therefore, methods designed to detect such traces have to be capable of detecting heat-treated peanuts. Commonly used methodologies designed to detect peanut traces in food products are enzyme-linked immunosorbent assays (ELISAs) that detect peanut-specific proteins, and polymerase-chain-reaction (PCR)-based methods targeting peanut-specific DNA. A comparative analysis of such methods was performed and the impact of heat treatment on peanut kernels as well as the impact on a peanut-containing food matrix are investigated. Our results show that heat treatments have a detrimental effect on the detection of peanut with either type of method and that both types of methods are affected in a similar manner. PMID- 19475404 TI - Phototransformations of selected pharmaceuticals under low-energy UVA-vis and powerful UVB-UVA irradiations in aqueous solutions--the role of natural dissolved organic chromophoric material. AB - The kinetics of simulated low-energy daylight (UVA-vis) and powerful combined ultraviolet B and A (UVB-UVA) induced direct and indirect phototransformations of four pharmaceuticals, i.e., ibuprofen, metoprolol, carbamazepine, and warfarin, which were investigated in dilute solutions of pure laboratory and natural humic waters. The results strengthen the essential function of natural chromophores in dissolved organic material (CDOM) as principal photosensitizer toward indirect phototransformations of pharmaceuticals in natural conditions under available low energy UVA-vis and slight UVB radiations. The results confirmed that organic micropollutants are able to undergo a direct photolysis if their absorbance spectra overlap the spectral range of the available radiation but only if the radiation is strong enough, e.g., ibuprofen is able to undergo only indirect photolysis via different pathways in all realistic conditions. The action of nitrate anions as photosensitizers in the applied conditions proved to be of little importance. High-performance size-exclusion chromatographic experiments verified that the rate constants obtained under the low-energy UVA-vis and powerful UVB-UVA irradiations for the decreased amounts of the two largest molecular size fractions of CDOM were quite close to the rate constants detected for the increased amounts of the next five molecular size fractions with smaller molecular sizes. The decreased contents of the two largest molecular size fractions correlated quite well with the decreased contents of the studied pharmaceuticals under the low-energy UVA-vis irradiation process but somewhat less under the powerful UVB-UVA irradiation. The photochemically induced decomposition of the CDOM aggregates appears to increase the amounts of smaller molecular size fractions and simultaneously produce via CDOM-stimulated radical reactions indirect structural transformations of pharmaceuticals. Apparent quantum yields were estimated for the transformation-degradation of the two largest molecular-size CDOM aggregates under low-energy UVA-vis and powerful UVB UVA irradiations. PMID- 19475405 TI - An innovative consecutive batch fermentation process for very high gravity ethanol fermentation with self-flocculating yeast. AB - An innovative consecutive batch fermentation process was developed for very high gravity (VHG) ethanol fermentation with the self-flocculating yeast under high biomass concentration conditions. On the one hand, the high biomass concentration significantly shortened the time required to complete the VHG fermentation and the duration of yeast cells suffering from strong ethanol inhibition, preventing them from losing viability and making them suitable for being repeatedly used in the process. On the other hand, the separation of yeast cells from the fermentation broth by sedimentation instead of centrifugation, making the process economically more competitive. The VHG medium composed of 255 g L(-1) glucose and 6.75 g L(-1) each of yeast extract and peptone was fed into the fermentation system for nine consecutive batch fermentations, which were completed within 8-14 h with an average ethanol concentration of 15% (v/v) and ethanol yield of 0.464, 90.8% of its theoretical value of 0.511. The average ethanol productivity that was calculated with the inclusion of the downstream time for the yeast flocs to settle from the fermentation broth and the supernatant to be removed from the fermentation system was 8.2 g L(-1) h(-1), much higher than those previously reported for VHG ethanol fermentation and regular ethanol fermentation with ethanol concentration around 12% (v/v) as well. PMID- 19475401 TI - From drugs to deprivation: a Bayesian framework for understanding models of psychosis. AB - INTRODUCTION: Various experimental manipulations, usually involving drug administration, have been used to produce symptoms of psychosis in healthy volunteers. Different drugs produce both common and distinct symptoms. A challenge is to understand how apparently different manipulations can produce overlapping symptoms. We suggest that current Bayesian formulations of information processing in the brain provide a framework that maps onto neural circuitry and gives us a context within which we can relate the symptoms of psychosis to their underlying causes. This helps us to understand the similarities and differences across the common models of psychosis. MATERIALS AND METHODS: The Bayesian approach emphasises processing of information in terms of both prior expectancies and current inputs. A mismatch between these leads us to update inferences about the world and to generate new predictions for the future. According to this model, what we experience shapes what we learn, and what we learn modifies how we experience things. DISCUSSION: This simple idea gives us a powerful and flexible way of understanding the symptoms of psychosis where perception, learning and inference are deranged. We examine the predictions of the cognitive model in light of what we understand about the neuropharmacology of psychotomimetic drugs and thereby attempt to account for the common and the distinctive effects of NMDA receptor antagonists, serotonergic hallucinogens, cannabinoids and dopamine agonists. CONCLUSION: By acknowledging the importance of perception and perceptual aberration in mediating the positive symptoms of psychosis, the model also provides a useful setting in which to consider an under researched model of psychosis-sensory deprivation. PMID- 19475406 TI - Biosynthesis and biotechnological production of flavanones: current state and perspectives. AB - Polyphenols produced in a wide variety of flowering and fruit-bearing plants have the potential to be valuable fine chemicals for the treatment of an assortment of human maladies. One of the major constituents within this chemical class are flavonoids, among which flavanones, as the precursor to all flavonoid structures, are the most prevalent. We review the current status of flavanone production technology using microorganisms, with focus on heterologous protein expression. Such processes appear as attractive production alternatives for commercial synthesis of these high-value chemicals as traditional chemical, and plant cell cultures have significant drawbacks. Other issues of importance, including fermentation configurations and economics, are also considered. PMID- 19475407 TI - Fixation of basicervical and related fractures. AB - We prospectively studied 42 patients in order to identify a group of proximal femoral fractures having liability for axial and rotational instability, and to present results of their fixation using the dynamic hip screw (DHS) with derotation screw (DRS). At 12 months postoperatively, patients were functionally evaluated and the radiological outcome was analysed. All fractures united within an average period of 11.5 weeks. The mean sliding distance was 5.5 mm and mean shortening of the limbs was 2 mm. According to the criteria of Kyle et al. (J Bone Joint Surg [Am] 61-A:216-221), 39 patients obtained excellent results, two good and one fair. We conclude that the AO types B2.1, A1.1, A2.1, A2.2 and A2.3 have a common instability denominator and therefore should be treated alike. The sliding component of the DHS allows solid fixation of the two major fragments in two planes and the DRS in the third plane. PMID- 19475408 TI - Pattern of limb amputation in a Kenyan rural hospital. AB - Causes of limb amputations vary between and within countries. In Kenya, reports on prevalence of diabetic vascular amputations are conflicting. Kikuyu Hospital has a high incidence of diabetic foot complications whose relationship with amputation is unknown. This study aimed to describe causes of limb amputations in Kikuyu Hospital, Kenya. Records of all patients who underwent limb amputation between October 1998 and September 2008 were examined for cause, age and gender. Data were analysed using the statistical package for Social Sciences (SPSS) for Windows Version 11.50. One hundred and forty patients underwent amputation. Diabetic vasculopathy accounted for 11.4% of the amputations and 69.6% of the dysvascular cases. More prevalent causes were trauma (35.7%), congenital defects (20%), infection (14.3%) and tumours (12.8%). Diabetic vasculopathy, congenital defects and infection are major causes of amputation. Control of blood sugar, foot care education, vigilant infection control and audit of congenital defects are recommended. PMID- 19475409 TI - Treatment of K562 cells with 1,25-dihydroxyvitamin D3 induces distinct alterations in the expression of apoptosis-related genes BCL2, BAX, BCLXL, and p21. AB - Apoptosis, or programmed cell death, is a very important phenomenon in cytotoxicity induced by anticancer treatment. 1alpha,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), the active metabolite of vitamin D, inhibits the growth of multiple types of cancer cells including breast, colon, and prostate cancer cell lines. We studied alterations in the mRNA expression levels of BCL2, BAX, CYC, BCL-XL, and VDR genes in the K562 chronic myeloid leukemia cell line in response to treatment with 1,25-(OH)(2)D(3). Morphological observation of K562 cells was evaluated by the staining with Wright's solution. Cell percentage at different phases of the cell cycle was measured, and apoptosis was measured by flow cytometry. The expression levels of the apoptosis-related genes were analyzed by real-time reverse transcription polymerase chain reaction. We found that treatment with 1,25-(OH)(2)D(3) down-regulates BCL2 and BCL-XL mRNA expressions, as well as up-regulates expressions of BAX and p21 mRNA. The expression pattern of CYC and VDR genes were not influenced. However, K562 cells treated with 1,25 (OH)(2)D(3) caused an arrest of cell cycle progression in G1 phase resulting in a decreased number of cells in the S phase, complemented by an accumulation of cells in the G0-G1 phases. Our data show the modulatory effects of 1,25 (OH)(2)D(3) treatment in apoptosis-related genes in K562 cells. PMID- 19475410 TI - Comparison of two sodium phosphate tablet-based regimens and a polyethylene glycol regimen for colon cleansing prior to colonoscopy: a randomized prospective pilot study. AB - PURPOSE: The aim of this pilot study was to compare the performance and safety of the newly developed sodium phosphate (NaP) tablet (with and without laxatives) and polyethylene glycol (PEG), as bowel-cleansing regimens prior to colonoscopy. METHODS: A total of 35 patients were randomized to one of the following three groups: NaP + laxative, NaP, or PEG. Quality of colon cleansing was assessed using a validated four-point scale, and the primary outcome measures were the mean overall colon cleansing and microcrystalline cellu1ose (MCC)-remaining scores in each group. RESULTS: The mean elapsed time for bowel cleansing in the NaP + laxative group (167.72 +/- 21.37 min) was significantly less than in the NaP group (218.00 +/- 20.58 min) and the PEG group (202.00 +/- 27.91 min; n = 11, 10, and 10 respectively; P < 0.05). The NaP + laxative group showed a superior overall colon-cleansing score compared to both the NaP and PEG groups and similarly, the overall colon MCC-remaining score in the NaP + laxative group was superior to the NaP group. Serum levels of inorganic phosphorus were significantly increased to abnormal levels in the NaP + laxative and NaP groups, but these increases were only transient. CONCLUSIONS: This pilot study shows that NaP-based bowel preparations are easy, quick, and safe to use. Colonoscopic visualization is decreased by MCC when NaP is used alone but is improved by the addition of laxatives on the previous day. A larger study is necessary to statistically verify these results. PMID- 19475411 TI - Evaluation of intraperitoneal lavage cytology before colorectal cancer resection. AB - PURPOSE: The aim of this study was to assess the usefulness of intraperitoneal lavage cytology (lavage Cy) status before the resection of colorectal cancer as a predictive factor of peritoneal recurrence. MATERIALS AND METHODS: The lavage Cy positive [lavage Cy (+)] rate, peritoneal recurrence rate, and 5-year survival rate were examined in 298 cases of colorectal cancer in relation to various clinicopathological factors. RESULTS: The overall lavage Cy (+) rate was 6.0%. The lavage Cy (+) rate within the group with peritoneal and hepatic metastases was significantly higher than that in the group without metastases (46.7% vs. 3.9% and 26.9% vs. 4.0%, respectively). The lavage Cy (+) rate was not significantly associated with any of the clinicopathological factors examined. The peritoneal recurrence rate was higher in the lavage Cy (+) group than in the lavage Cy-negative [lavage Cy (-)] group, although the difference was not statistically significant. There was no significant difference in survival, regardless of the lavage Cy status, among the 263 patients who underwent curative resection. CONCLUSION: The lavage Cy status before resection was not a useful predictive factor of peritoneal recurrence in cases of colorectal cancer. PMID- 19475412 TI - The place of ultrasound in urogynaecology clinic. AB - Urinary incontinence is a silent epidemic severely affecting the quality of life of women. Clinical assessment alone has been shown to be an ineffective way of assessing women with lower urinary tract dysfunction; hence, there is a need for urodynamic studies. Nevertheless, urodynamics cannot explain all the symptoms and is not always available. Ultrasound scan is becoming more useful in the field of urogynaecology. It is safe, non-invasive and acceptable technique for the patients. In this review, we explore the place of modern ultrasound in managing women attending urogynaecology clinic. PMID- 19475413 TI - Progesterone levels in cesarean and normal delivered term placentas. AB - BACKGROUND: One of the most important hormones synthesized by the placenta during pregnancy is progesterone. The regulating mechanisms of progesterone synthesis and the mechanism responsible for the spontaneous onset of labor in women are still not fully understood. Progesterone is thought to have been involved in human parturition. The objective of this study was to compare the levels of progesterone in the human placentas, at the end of the gestation (37-41 weeks) in vaginal versus cesarean deliveries, and to evaluate the pattern of progesterone accumulation, instantly following its synthesis by the human placenta at the end of the pregnancy. METHODS: Progesterone levels in human placental tissue were determined by immunochemiluminescent analysis, following tissue homogenization. Progesterone secretion and accumulation pattern in the placental tissue was demonstrated using the ex vivo, closed, dual perfusion system of isolated human placental cotyledon. RESULTS: Immunochemiluminescent analysis of progesterone levels in human normal and cesarean-delivered placentas showed that placentas following normal vaginal delivery store higher concentrations of progesterone, and produce progesterone more intensively. Results obtained from 120-min perfusions (of vaginal and cesarean-delivered placentas) showed that progesterone tended to accumulate in the maternal rather than the fetal compartment. CONCLUSIONS: These data indicate that progesterone levels continuously rise till the end of pregnancy, with no apparent drop in progesterone levels during the labor process. In addition, progesterone is released from the syncytiotrophoblast preferably into the maternal component of the placental tissue. PMID- 19475414 TI - Incidence of leukaemia and other malignant diseases following injections of the short-lived alpha-emitter 224Ra into man. AB - We performed an epidemiological study on 1,471 ankylosing spondylitis patients treated with repeated intravenous injections of the short lived alpha-emitter (224)Ra (excluding radiation therapy with X-rays) between 1948 and 1975. These patients have been followed together with a control group of 1,324 ankylosing spondylitis patients treated neither with radioactive drugs nor with X-rays. The mean follow-up time was 26.3 years in the exposed and 24.6 years in the control group. To date, causes of death have been ascertained for 1,006 exposed patients and 1,072 controls. Special emphasis was placed on the reporting of malignant diseases. Expected numbers of cases were computed for the age, sex and calendar year distribution of both groups using cancer registry incidence rates. In the exposed group 18 cases of kidney cancer (vs. 9.1 cases expected, P < 0.01) and 4 malignant thyroid tumours (vs. 1.2 cases expected, P = 0.03) were observed. In the control group the observed cases for these tumours were not significantly elevated. The most striking observation, however, were the 21 cases of leukaemia in the exposed group (vs. 6.8 cases expected, P < 0.001) compared to 12 cases of leukaemia in the control group (vs. 7.5 cases expected). Further sub classification of the leukaemias demonstrated a high increase of myeloid leukaemia in the exposed group (12 cases observed vs. 2.9 cases expected, P < 0.001), and out of these, especially a high excess of acute myeloid leukaemias (7 cases observed vs. 1.8 expected, P = 0.003). In the controls the observed cases are within the expected range (4 myeloid leukaemias vs. 3.1 cases). This increase in total leukaemias as well as particularly in myeloid leukaemias is significant in direct comparison between the exposed and control groups too (P < 0.05). The enhanced leukaemia incidence in the exposed group is in line with the observation of increased leukaemia incidence in mice injected with (224)Ra. PMID- 19475415 TI - Clinical review of corneal ulcers resulting in evisceration and enucleation in elderly population. AB - PURPOSE: To identify the associated factors and study the clinical and microbiological characteristics of corneal ulcers resulting in evisceration and enucleation in elderly patients in a tertiary care hospital. METHODS: A review of all patients who required evisceration or enucleation due to microbial keratitis at the Royal Victorian Eye and Ear Hospital, Melbourne, Australia between July 1998 and November 2007 was performed. Of these, patients more than 60 years of age were included in the study for analysis. RESULTS: Forty-seven patients with microbial keratitis were included in the study. The mean age of patients was 81 +/- 9.39 years. Major ocular factors associated were glaucoma (49%), persistent corneal epithelial defect (38%) and use of corticosteroid eye drops (23%). Most common associated systemic factor was rheumatoid arthritis (36%). The indications for evisceration or enucleation were extensive non-healing microbial keratitis (22/47) and corneal perforation secondary to microbial keratitis (17/47). Pseudomonas aeruginosa was the most common pathogen, present in 15 patients, and more than 45% of the strains tested were resistant to chloramphenicol. CONCLUSIONS: Corneal ulcers that result in the loss of eye in elderly population are frequently associated with glaucoma and persistent epithelial defects. The majority of these cases have non-healing microbial keratitis caused by Pseudomonas aeruginosa. PMID- 19475416 TI - TMEM16B induces chloride currents activated by calcium in mammalian cells. AB - Ca(2+)-activated Cl(-) channels play important physiological roles in various cell types, but their molecular identity is still unclear. Recently, members of the protein family named transmembrane 16 (TMEM16) have been suggested to function as Ca(2+)-activated Cl(-) channels. Here, we report the functional properties of mouse TMEM16B (mTMEM16B) expressed in human embryonic kidney (HEK) 293T cells, measured both in the whole-cell configuration and in inside-out excised patches. In whole cell, a current induced by mTMEM16B was activated by intracellular Ca(2+) diffusing from the patch pipette, released from intracellular stores through activation of a G-protein-coupled receptor, or photoreleased from caged Ca(2+) inside the cell. In inside-out membrane patches, a current was rapidly activated by bath application of controlled Ca(2+) concentrations, indicating that mTMEM16B is directly gated by Ca(2+). Both in the whole-cell and in the inside-out configurations, the Ca(2+)-induced current was anion selective, blocked by the Cl(-) channel blocker niflumic acid, and displayed a Ca(2+)-dependent rectification. In inside-out patches, Ca(2+) concentration for half-maximal current activation decreased from 4.9 microM at 50 mV to 3.3 microM at +50 mV, while the Hill coefficient was >2. In inside-out patches, currents showed a reversible current decrease at -50 mV in the presence of a constant high Ca(2+) concentration and, moreover, an irreversible rundown, not observed in whole-cell recordings, indicating that some unknown modulator was lost upon patch excision. Our results demonstrate that mTMEM16B functions as a Ca(2+)-activated Cl(-) channel when expressed in HEK 293T cells. PMID- 19475417 TI - Defining features of the hair cell mechanoelectrical transducer channel. AB - This review summarizes current knowledge of the hair cell mechanotransducer channel, the ion channel responsible for detecting mechanical stimuli in the inner ear and one of the few channels whose molecular structure is still unknown. Several candidate proteins have been proposed, especially members of the transient receptor potential (TRP) channel family, but all have so far failed in one test or another. Furthermore, none has biophysical properties exactly matching the native channel. The defining features of the native mechanotransducer channel are documented, including ionic permeability, channel structure inferred from blocking agents, diversity in channel conductance, and regulation by Ca(2+), which are compared with a potential candidate, TRP channels of the polycystin family. The strengths and weaknesses of a TRP channel contender are discussed. PMID- 19475418 TI - The acid test: the discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels. AB - In this review, we describe the background and implications of our recent discovery that two-pore channels (TPCs) comprise a novel class of calcium release channels gated by the intracellular messenger nicotinic acid adenine dinucleotide phosphate (NAADP). Their localisation to the endolysosomal system highlights a new function for these organelles as targets for NAADP-mediated Ca(2+) mobilisation. In addition, we describe how TPCs may also trigger further Ca(2+) release by coupling to the endoplasmic reticular stores through activation of IP(3) receptors and ryanodine receptors. PMID- 19475420 TI - Induction of multinucleation by beta-glucosyl Yariv reagent in regenerated cells from Marchantia polymorpha protoplasts and involvement of arabinogalactan proteins in cell plate formation. AB - Arabinogalactan proteins (AGPs) are abundant plant cell surface proteoglycans widely distributed in plant species. Since high concentrations of beta-glucosyl Yariv reagent (betaglcY), which binds selectively to AGPs, inhibited cell division of protoplast-regenerated cells of the liverwort Marchantia polymorpha L. (Shibaya and Sugawara in Physiol Plant 130:271-279, 2007), we investigated the mechanism underlying the inability of the cells to divide normally by staining nuclei, cell walls and beta-1,3-glucan. Microscopic observation showed that the diameter of regenerated cells cultured with betaglcY was about 2.8-fold larger than that of cells cultured without betaglcY. The cells cultured with betaglcY were remarkably multinucleated. These results indicated that betaglcY did not inhibit mitosis but induced multinucleation. In the regenerated cells cultured with low concentrations of betaglcY (5 and 1 microg ml(-1)), the cell plate was stained strongly by betaglcY, suggesting abundant AGPs in the forming cell plate. In these cell plates, beta-1,3-glucan was barely detectable or not detected. In multinucleated cells, cell plate-like fragments, which could not reach the cell wall, were frequently observed and they were also stained strongly by betaglcY. Our results indicated that AGPs might have an important role in cell plate formation, and perturbation of AGPs with betaglcY might result in remarkable multinucleation in protoplast-regenerated cells of M. polymorpha. PMID- 19475419 TI - Stress-induced curcin-L promoter in leaves of Jatropha curcas L. and characterization in transgenic tobacco. AB - Ribosome-inactivating proteins (RIPs) represent a type of protein that universally inactivates the ribosome thus inhibiting protein biosynthesis. Curcin L was a type I RIP found in Jatropha curcas L.. Its expression could be activated in leaves by treatments with abscisic acid, salicylic acid, polyethylene glycol, temperature 4, 45 degrees C and ultraviolet light. A 654 bp fragment of a 5' flanking region preceding the curcin-L gene, designated CP2, was cloned from the J. curcas genome and its expression pattern was studied via the expression of the beta-glucuronidase (GUS) gene in transgenic tobacco. Analysis of GUS activities showed that the CP2 was leaf specific, and was able to drive the expression of the reporter gene under stress-induction conditions. Analysis of a series of 5' deletions of the CP2 suggested that several promoter motifs were necessary to respond to environmental stresses. PMID- 19475421 TI - Clinical practice: the spine from birth to adolescence. AB - The spine in children can be affected by different bone pathologies such as trauma, infection, and tumoral processes. Most typical however are postural deformities, of which the evolution is mainly influenced by growth. An overview will be given of the most frequent problems encountered in children. Back pain is not infrequent and should always be taken seriously. In recent years, however, there has been an increase in functional complaints, mainly due to stress-related problems. Improving imaging techniques allows more and more accurate diagnoses and should be used judiciously. Postural deformities should be divided into functional and structural entities. Functional hyperkyphosis, hyperlordosis, and scoliosis should be identified by a thorough clinical evaluation and certainly not be overtreated. A structural scoliosis has the most potential of creating cardiovascular or pain problems in later life. Not all curves however have a bad prognosis. It is the task of the clinician to identify the children needing special attention, based on their knowledge of the underlying pathology as in congenital scoliosis and of the physiological age or maturity of the child, especially in the adolescent idiopathic scoliosis. Treatment should be initiated according to the prognosis regardless of the age of the child. PMID- 19475422 TI - Characteristics associated with maltreatment types in children referred to a hospital protection team. AB - OBJECTIVE: The aim of this paper is to describe characteristics associated with maltreatment types in children referred to the child protection team at the University Children's Hospital Zurich. Since 2003, the child protection team has registered data on each case in a standardized form. METHODS: To examine differences in gender, age, nationality, and socioeconomic status by type of maltreatment, regression analyses were conducted for the 1,484 cases that were referred from 2003 to 2006. RESULTS: The most common types of referred maltreatment were sexual (38%) and physical maltreatment (31%) with mean ages of 8.4 and 7 years, respectively. Compared to physical maltreatment, where gender distribution was equal, there was a higher risk for girls to become victims of sexual maltreatment. Younger children were at higher risk for neglect (mean age 5 years). Low socioeconomic status increased the risk for physical as compared to sexual maltreatment. However, whether the child was of Swiss or of foreign nationality was not associated with an increased risk for any type of maltreatment when controlling for socioeconomic status. CONCLUSION: As this study is one of a few to analyze characteristics in child maltreatment referred to a hospital child protection team, further research is needed. To improve international comparability, thorough documentation of the cases is encouraged. PMID- 19475423 TI - Effects of temperature, salinity, and water level on the emergence of marine cercariae. AB - With the prospect of large-scale environmental changes, there is an urgent need to obtain information regarding environmental influences acting on the emergence of cercariae in marine systems. We investigated the response of trematodes of the intertidal snail Zeacumantus subcarinatus to altered temperature, salinity, and water level. The emergence of one trematode species, Maritrema novaezealandensis (Microphallidae), showed a weak trend to decrease with increased temperature; whereas, the emergence of a second species, Philophthalmus sp. (Philophthalmidae), increased at warmer temperatures. Both species exhibited increased cercarial emergence at the lowest salinity used (30 PSU). More M. novaezealandensis cercariae emerged when snails were kept partially submerged. In contrast, emergence of Philophthalmus sp. increased when snails were completely submerged. These results may reflect different transmission strategies employed by the two trematode species. Based on this model, we propose that trematode parasitism in intertidal zones is likely to be impacted by various changes in the marine environment resulting from global warming. PMID- 19475424 TI - Cordial connections: molecular ensembles and structures of adhering junctions connecting interstitial cells of cardiac valves in situ and in cell culture. AB - Remarkable efforts have recently been made in the tissue engineering of heart valves to improve the results of valve transplantations and replacements, including the design of artificial valves. However, knowledge of the cell and molecular biology of valves and, specifically, of valvular interstitial cells (VICs) remains limited. Therefore, our aim has been to determine and localize the molecules forming the adhering junctions (AJs) that connect VICs in situ and in cell culture. Using biochemical and immunolocalization methods at the light- and electron-microscopic levels, we have identified, in man, cow, sheep and rat, the components of VIC-connecting AJs in situ and in cell culture. These AJs contain, in addition to the transmembrane glycoproteins N-cadherin and cadherin-11, the typical plaque proteins alpha- and beta-catenin as well as plakoglobin and p120, together with minor amounts of protein p0071, i.e. a total of five plaque proteins of the armadillo family. While we can exclude the occurrence of desmogleins, desmocollins and desmoplakin, we have noted with surprise that AJs of VICs in cell cultures, but not those growing in the valve tissue, contain substantial amounts of the desmosomal plaque protein, plakophilin-2. Clusters of AJs occur not only on the main VIC cell bodies but are also found widely dispersed on their long filopodia thus forming, in the tissue, a meshwork that, together with filopodial attachments to paracrystalline collagen fiber bundles, establishes a three-dimensional suprastructure, the role of which is discussed with respect to valve formation, regeneration and function. PMID- 19475425 TI - Glycerol triacetate as solvent and acyl donor in the production of isoamyl acetate with Candida antarctica lipase B. AB - Glycerol triacetate was successfully used as a green solvent and as the acyl donor in the transesterification of isoamyl alcohol to produce isoamyl acetate using free and immobilized Candida antarctica lipase B. Immobilized lipase was more catalytically active than free lipase and could be easily separated from the reaction mixture by filtration. In addition, it was found that increasing either the reaction temperature or the enzyme to substrate ratio increased the conversion of isoamyl alcohol. Using triacetin as the solvent also enabled the separation of product by simple extraction with petroleum ether and catalyst recycling. PMID- 19475426 TI - Serum cystatin C as a possible marker to detect renal maturation. PMID- 19475427 TI - Acute renal failure due to obstructive uric acid stones associated with acute gastroenteritis. PMID- 19475428 TI - Use of recombinant human serum albumin in pediatric patients with nephrotic syndrome. PMID- 19475429 TI - Correlation between fat mass and blood pressure in healthy children. AB - Obesity is a well-known risk factor for arterial hypertension. The aim of this study was to analyze which surrogate marker of adiposity, i.e., body mass index (BMI) or fat mass (FM), as measured by bioimpedance analysis (BIA), best correlated with blood pressure in healthy children. Body weight, height, and casual blood pressure (BP) were measured in 193 healthy children (103 boys), aged 8-16 years. Body composition was determined by BIA. The correlation between BMI and age was linear, whereas the correlation between percentage of FM and age was nonlinear and it was different in boys and girls. Blood pressure standard deviation scores (SDS) correlated with FM SDS (BIA) over the entire normal range (systolic: r = 0.26, p = 0.002; diastolic: r = 0.33, p < 0.01). An evaluation of the children based on BP (three groups: BP < 50th percentile, 50th < BP > 95th percentile; BP > 95th percentile) revealed that hypertensive children had a higher BMI (17.6 vs. 19.4 vs. 26.2 kg/m(2), respectively) and a greater FM (14.0 vs. 16.8 vs. 30.2%, respectively). In conclusion, the divergence in FM in healthy boys and girls can be determined by BIA but not by BMI. In healthy children, BP within the entire normal range correlated with FM, children with established hypertension presented with a significantly higher FM. The study points to FM as an important determinant of BP pressure in obese and non-obese children. PMID- 19475430 TI - Juvenile linear scleroderma with unique forms of renal involvement. AB - Linear scleroderma is the most common type of juvenile localized scleroderma, which usually involves the limbs. The linear lesions may extend through the dermis, subcutaneous tissue, muscles, and the underlying bone, leading to significant functional and cosmetic deformities. Renal involvement in juvenile localized scleroderma is a rare manifestation. Here we report two cases with juvenile linear scleroderma and unique renal manifestations, including unilateral renal arterial stenosis and immunoglobulin M nephropathy. PMID- 19475431 TI - The effect of obesity on kidney length in a healthy pediatric population. AB - Over the past decade, the percentage of children who are obese has rapidly increased. As weight has been shown to correlate strongly with the size of various organs, we have observed that obese children have larger kidneys than their normal-weight counterparts. This study sought to quantify this observation by establishing the normal limits of renal length for this population. We examined 204 healthy patients seen for benign hematuria between January 2000 and May 2008. Both right and left kidney lengths significantly correlated with age, height, weight, body mass index and body surface area in our obese patients (n = 59). Height was also found to be a significant predictor of kidney length, in the obese group, by multiple linear regression analysis and was used to create renal length nomograms for the obese pediatric population (P < 0.01). According to this analysis, obese patients had significantly larger kidneys than those of normal weight patients (P < 0.01). By defining the normal limits of renal length for this group, unnecessary evaluation for nephromegaly will be avoided. PMID- 19475432 TI - Heat shock proteins in children and young adults on chronic hemodialysis. AB - Chronic inflammation, lipid and autoimmune disorders are hallmarks of atherogenesis, and hemodialysis per se may be an additional factor predisposing to accelerated atherosclerosis. Elevated levels of heat shock proteins (HSP) and antibodies against these HSP have been described in adults with atherosclerotic lesions and cardiovascular events, but to date there has been a scarcity of investigations on these parameters in adult and pediatric patients on hemodialysis (HD). We have investigated the HSP profile in hemodialyzed children and the impact of a single HD session on those proteins and their correlations with known risk factors for atherosclerosis. The study group consisted of 17 children and young adults undergoing HD with polysulfone membranes. The control group comprised 15 age-matched subjects with normal kidney function. The serum concentrations of Hsp60, Hsp90alpha, anti-Hsp60, anti-Hsp70, and sE-selectin were assessed by an enzyme-linked immunosorbent assay, and serum concentration of high sensitivity-C-reactive protein was assayed by nephelometry. The serum lipid profile [total cholesterol (CHOL), high-density lipoprotein-CHOL, low-density lipoprotein-CHOL, triglycerides] was also estimated. Compared to the control values, the median values of Hsp60 before the HD session were lower, whereas those of Hsp90alpha and anti-Hsp60 were higher. A single HD session raised the median values of Hsp60 and Hsp90alpha and decreased the concentrations of anti Hsp60 and anti-Hsp70. In addition, the concentrations of HSPs and the antibodies against them correlated with the lipid markers both before and after HD. The altered HSP and anti-HSP concentrations in HD children, which correlated with the lipid profile and the endothelial markers, suggest a dysfunctional HSP system in this population and the possibility of HSPs being classified as new markers of atherosclerosis. PMID- 19475433 TI - Quality of life of adolescents with end-stage renal disease and kidney transplant. AB - The health-related quality of life (HRQOL) of adolescents with end-stage renal disease (ESRD) is an important marker of disease burden. Our aims were to investigate HRQOL in a group of children and adolescents with ESRD and to compare them with the reference population norms. Ours was a cross-sectional study of 81 patients aged 10 years to 21 years with ESRD (68 with kidney transplants and 13 on dialysis) at five Spanish paediatric nephrology centres. HRQOL was investigated with the Spanish version of the child health and illness profile, adolescent edition (CHIP-AE). Clinical variables such as underlying diagnosis, number of rejection episodes, pre-emptive transplantation, anaemia and height were also analysed. No differences were found between patients with kidney transplants and their healthy peers in any domain or sub-domain of CHIP-AE. The group on dialysis scored lower than healthy controls and patients with transplants for satisfaction with health. Discomfort was higher in patients with transplants who had suffered one rejection episode. Physical discomfort was increased in anaemic patients with transplants. Short patients scored less in the satisfaction domain, with lower self-esteem and lower satisfaction with health. Adolescents with kidney transplants had better satisfaction with health than the group on dialysis, which matched the level of a healthy population. Further long term prospective research is warranted. PMID- 19475434 TI - The use of RhBMP-2 in single-level transforaminal lumbar interbody fusion: a clinical and radiographic analysis. AB - The "off label" use of rhBMP-2 in the transforaminal lumbar interbody fusion (TLIF) procedure has become increasingly popular. Although several studies have demonstrated the successful use of rhBMP-2 for this indication, uncertainties remain regarding its safety and efficacy. The purpose of this study is to evaluate the clinical and radiographic outcomes of the single-level TLIF procedure using rhBMP-2. Patients who underwent a single-level TLIF between January 2004 and May 2006 with rhBMP-2 were identified. A retrospective evaluation of these patients included operative report(s), pre- and postoperative medical records, and dynamic and static lumbar radiographs. Patient-reported clinical outcome measures were obtained from a telephone questionnaire and included a modification of the Odom's criteria, a patient satisfaction score, and back and leg pain numeric rating scale scores. Forty-eight patients met the study criteria and were available for follow-up (avg. radiographic and clinical follow up of 19.4 and 27.4 months, respectively). Radiographic fusion was achieved in 95.8% of patients. Good to excellent results were achieved in 71% of patients. On most recent clinical follow-up, 83% of patients reported improvement in their symptoms and 84% reported satisfaction with their surgery. Twenty-nine patients (60.4%) reported that they still had some back pain, with an average back pain numeric rating score of 2.8. Twenty patients (41.7%) reported that they still had some leg pain, with an average leg pain numeric rating score was 2.4. Thirteen patients (27.1%) had one or more complications, including transient postoperative radiculitis (8/48), vertebral osteolysis (3/48), nonunion (2/48), and symptomatic ectopic bone formation (1/48). The use of rhBMP-2 in the TLIF procedure produces a high rate of fusion, symptomatic improvement and patient satisfaction. Although its use eliminates the risk of harvesting autograft, rhBMP-2 is associated with other complications that raise concern, including a high rate of postoperative radiculitis. PMID- 19475435 TI - Reviewer's comment concerning "Anterior cervical pedicle screw and plate fixation using fluoroscope-assisted pedicle axis view imaging: a preliminary report of a new cervical reconstruction technique" by Y. Yukawa et al.: DOI:10.1007/s00586 009-0949-1. PMID- 19475436 TI - The influence of cage positioning and cage type on cage migration and fusion rates in patients with monosegmental posterior lumbar interbody fusion and posterior fixation. AB - In posterior lumbar interbody fusion, cage migrations and lower fusion rates compared to autologous bone graft used in the anterior lumbar interbody fusion procedure are documented. Anatomical and biomechanical data have shown that the cage positioning and cage type seem to play an important role. Therefore, the aim of the present study was to evaluate the impact of cage positioning and cage type on cage migration and fusion. We created a grid system for the endplates to analyze different cage positions. To analyze the influence of the cage type, we compared "closed" box titanium cages with "open" box titanium cages. This study included 40 patients with 80 implanted cages. After pedicle screw fixation, 23 patients were treated with a "closed box" cage and 17 patients with an "open box" cage. The follow-up period averaged 25 months. Twenty cages (25%) showed a migration into one vertebral endplate of <3 mm and four cages (5%) showed a migration of > or =3 mm. Cage migration was highest in the medio-medial position (84.6%), followed by the postero-lateral (42.9%), and the postero-medial (16%) cage position. Closed box cages had a significantly higher migration rate than open box cages, but fusion rates did not differ. In conclusion, cage positioning and cage type influence cage migration. The medio-medial cage position showed the highest migration rate. Regarding the cage type, open box cages seem to be associated with lower migration rates compared to closed box cages. However, the cage type did not influence bone fusion. PMID- 19475437 TI - Posterolateral spinal fusion in a rabbit model using a collagen-mineral composite bone graft substitute. AB - Choosing the appropriate graft material to participate in the healing process in posterolateral spinal fusion continues to be a challenge. Combining synthetic graft materials with bone marrow aspirate (BMA) and autograft is a reasonable treatment option for surgeons to potentially reduce or replace the need for autograft. FormaGraft, a bone graft material comprising 12% bovine-derived collagen and 88% ceramic in the form of hydroxyapatite (HAp) and beta tricalcium phosphate (beta-TCP) was evaluated in three possible treatment modalities for posterior spinal fusion in a standard rabbit model. These three treatment groups were FormaGraft alone, FormaGraft soaked in autogenous BMA, and FormaGraft with BMA and iliac crest autograft. No statistically demonstrable benefits or adverse effects of the addition of BMA were found in the current study based on macroscopic, radiology or mechanical data. This may reflect, in part, the good to excellent results of the collagen HA/TCP composite material alone in a well healing bony bed. Histology did, however, reveal a benefit with the use of BMA. Combining FormaGraft with autograft and BMA achieved results equivalent to autograft alone. The mineral and organic nature of the material provided a material that facilitated fusion between the transverse processes in a standard preclinical posterolateral fusion model. PMID- 19475439 TI - The economics of cochlear implant management in France: a multicentre analysis. AB - This study assessed the direct medical cost of cochlear implantation in children and adults in France. A prospective multicentre study involving 19 French University Hospitals included 268 children and 201 adults who were severely to profoundly hearing-impaired. Medical resources utilisation included diagnostic tests, in-patient care, device implants, adverse events and follow-up visits for rehabilitation in the 1st year. The mean costs were 34,686 per child and 31,946 per adult. The cost of device implant represents 64.4% and 68.8% of the total cost for children and adults, respectively. The current reform of financing of the healthcare system requires detailed knowledge of the costs of interventions, hence the costs of cochlear implantation should be factored into resource allocation decisions. Differences in our results compared to other studies can be explained mostly by methodological differences in cost analyses. PMID- 19475438 TI - U1 snRNA mis-binding: a new cause of CMT1B. AB - We report the molecular characterization of two splice mutations in two different French families affected with a late onset form of Charcot-Marie-Tooth disease type 1B (CMT1B), an autosomal dominant inherited disorder caused by mutations in the myelin protein zero gene. The first substitution, c.306G>A, located in exon 3, does not change the codon p.Val102Val but is co-transmitted with the disease in the first family. The second substitution, c.675+3dup, is an insertion of a T at position +3 of intron 5. To identify the functional impact of these nucleotide changes on splicing and because no RNA sample was available, we used in silico prediction and in vitro splicing assay. Mutation c.306G>A increases the strength of a preexisting cryptic donor site at position c.304 which becomes stronger than the normal donor site of intron 3. This variation creates a sequence that better matches the U1 small nuclear RNA (snRNA) binding consensus, and HeLa cells, transfected with the mutant minigene, produce a truncated exon 3 messenger RNA (mRNA). Mutation c.675+3dup was predicted to abolish the donor site of intron 5, and, indeed, HeLa cells transfected with the mutant minigene completely skip exon 5 from the transcript. The mutated sequence abolishes U1 snRNA binding and co transfection of a mutated complementary U1 snRNA restored exon 5 inclusion in the mRNA. This work provides valuable information regarding the molecular basis of two forms of late onset of CMT1B, U1 snRNA mis-binding, and provides more evidence that a "silent" polymorphism may be a disease causing mutation. PMID- 19475440 TI - Farmer knowledge and a priori risk analysis: pre-release evaluation of genetically modified Roundup Ready wheat across the Canadian prairies. AB - BACKGROUND, AIM, AND SCOPE: The controversy over the world's first genetically modified (GM) wheat, Roundup Ready wheat (RRW), challenged the efficacy of 'science-based' risk assessment, largely because it excluded the public, particularly farmers, from meaningful input. Risk analysis, in contrast, is broader in orientation as it incorporates scientific data as well as socioeconomic, ethical, and legal concerns, and considers expert and lay input in decision-making. Local knowledge (LK) of farmers is experience-based and represents a rich and reliable source of information regarding the impacts associated with agricultural technology, thereby complementing the scientific data normally used in risk assessment. The overall goal of this study was to explore the role of farmer LK in the a priori risk analysis of RRW. MATERIALS AND METHODS: In 2004, data were collected from farmers using mail surveys sent across the three prairie provinces (i.e., Manitoba, Saskatchewan, and Alberta) in western Canada. A stratified random sampling approach was used whereby four separate sampling districts were identified in regions where wheat was grown for each province. Rural post offices were randomly selected in each sampling district using Canada Post databases such that no one post office exceeded 80 farms and that each sampling district comprised 225-235 test farms (n = 11,040). In total, 1,814 people responded, representing an adjusted response rate for farmers of 33%. A subsequent telephone survey showed there was no non-response bias. RESULTS: The primary benefits associated with RRW were associated with weed control, whereas risks emphasized the importance of market harm, corporate control, agronomic problems, and the likelihood of contamination. Overall, risks were ranked much higher than benefits, and the great majority of farmers were highly critical of RRW commercialization. In total, 83.2% of respondents disagreed that RRW should have unconfined release into the environment. Risk was associated with distrust in government and corporations, previous experience with GM canola, and a strong belief in the importance of community and environment. Farmers were critical of expert-based risk assessment, particularly RRW field trials, and believed that their LK was valuable for assessing agbiotechnology as a whole. DISCUSSION: Over 90% of canola production across the Canadian prairies makes use of herbicide-tolerant (HT) varieties. Yet, respondents were generally uniform in their criticism of RRW, regardless whether they were HT users, non-HT users, conservation tillage or organic in approach. They had a sophisticated understanding of how GM trait confinement was intrinsically tied to grain system segregation and, ultimately, market accessibility, and were concerned that gene flow in RRW would not be contained. Organic farmers were particularly critical of RRW, in large part because certification standards prohibit the presence of GM traits. Farmers practicing conservation tillage were also at relatively great risk, in part because their dependence on glyphosate to control weeds increases the likelihood that RRW volunteer would become more difficult and costly to control. CONCLUSIONS: This research is the first of its kind to include farmer knowledge in the a priori risk analysis of GM crops and, arguably, given its prairie-wide scope, is the largest scale, independent-farmer-focused study on GM crops ever conducted. The surprising uniformity in attitudes between users and non-users of GM technology and among organic, conventional, conservation tillage and GM using farmers speaks to the ability of farmers to discriminate among HT varieties. Our results clearly show that prairie farmers recognize that the risks associated with RRW commercialization outweigh any benefits. RECOMMENDATIONS AND PERSPECTIVES: Farmer knowledge systems are holistic in nature, incorporating socioeconomic, cultural, political, and agroecological factors that all can contribute meaningfully to the pre-release evaluation of GM crops. The inclusion of farmers and other stakeholders in risk assessment will also help enhance and even restore public confidence in science-focused approaches to risk assessment. Although farmers are highly knowledgeable regarding RRW and arguably any agricultural technology, their expertise continues to be overlooked by decision makers and regulators across North America. PMID- 19475441 TI - Targeting aquatic microcontaminants for monitoring: exposure categorization and application to the Swiss situation. AB - BACKGROUND, AIM, AND SCOPE: Aquatic microcontaminants (MCs) comprise diverse chemical classes, such as pesticides, biocides, pharmaceuticals, consumer products, and industrial chemicals. For water pollution control and the evaluation of water protection measures, it is crucial to screen for MCs. However, the selection and prioritization of which MCs to screen for is rather difficult and complex. Existing methods usually are strongly limited because of a lack of screening regulations or unavailability of required data. METHOD AND MODELS: Here, we present a simple exposure-based methodology that provides a systematic overview of a broad range of MCs according to their potential to occur in the water phase of surface waters. The method requires input of publicly available data only. Missing data are estimated with quantitative structure property relationships. The presented substance categorization methodology is based on the chemicals' distribution behavior between different environmental media, degradation data, and input dynamics. RESULTS: Seven different exposure categories are distinguished based on different compound properties and input dynamics. Ranking the defined exposure categories based on a chemical's potential to occur in the water phase of surface waters, exposure categories I and II contain chemicals with a very high potential, categories III and IV contain chemicals with a high potential, and categories V and VI contain chemicals with a moderate to low potential. Chemicals in category VII are not evaluated because of a lack of data. We illustrate and evaluate the methodology on the example of MCs in Swiss surface waters. Furthermore, a categorized list containing potentially water-relevant chemicals is provided. DISCUSSION: Chemicals of categories I and III continuously enter surface waters and are thus likely to show relatively steady concentrations. Therefore, they are best suited for water monitoring programs requiring a relatively low sampling effort. Chemicals in categories II and IV have complex input dynamics. They are consequently more difficult to monitor. However, they should be considered if an overall picture is needed that includes contaminants from diffuse sources. CONCLUSIONS: The presented methodology supports compound selection for (a) water quality guidance, (b) monitoring programs, and (c) further research on the chemical's ecotoxicology. The results from the developed categorization procedure are supported by data on consumption and observed concentrations in Swiss surface waters. The presented methodology is a tool to preselect potential hazardous substances based on exposure-based criteria for policy guidance and monitoring programs and a first important step for a detailed risk assessment for potential microcontaminants. PMID- 19475442 TI - The complete mitochondrial genome sequence of the hornwort Megaceros aenigmaticus shows a mixed mode of conservative yet dynamic evolution in early land plant mitochondrial genomes. AB - Land plants possess some of the most unusual mitochondrial genomes among eukaryotes. However, in early land plants these genomes resemble those of green and red algae or early eukaryotes. The question of when during land plant evolution the dramatic change in mtDNAs occurred remains unanswered. Here we report the first completely sequenced mitochondrial genome of the hornwort, Megaceros aenigmaticus, a member of the sister group of vascular plants. It is a circular molecule of 184,908 base pairs, with 32 protein genes, 3 rRNA genes, 17 tRNA genes, and 30 group II introns. The genome contains many genes arranged in the same order as in those of a liverwort, a moss, several green and red algae, and Reclinomonas americana, an early-branching eukaryote with the most ancestral form of mtDNA. In particular, the gene order between mtDNAs of the hornwort and Physcomitrella patens (moss) differs by only 8 inversions and translocations. However, the hornwort mtDNA possesses 4 derived features relative to green alga mtDNAs--increased genome size, RNA editing, intron gains, and gene losses--which were all likely acquired during the origin and early evolution of land plants. Overall, this genome and those of other 2 bryophytes show that mitochondrial genomes in early land plants, unlike their seed plant counterparts, exhibit a mixed mode of conservative yet dynamic evolution. PMID- 19475443 TI - Right ventricular dysfunction and B-type natriuretic peptide in asymptomatic patients after repair for tetralogy of Fallot. AB - Early detection of right ventricular (RV) dysfunction is essential in the assessment of patients with repaired tetralogy of Fallot (TOF). This study aimed to assess latent RV dysfunction in asymptomatic patients with TOF and to determine the predictive value of B-type natriuretic peptide (BNP). Pressure volume loops were recorded for 16 young patients (New York Heart Association class 1 or Ross class 0; median age, 14.2 years) using the conductance catheter technique. All the patients had RV dilation secondary to pulmonary regurgitation after surgical repair of TOF. Indexes of RV function were derived at baseline level and during dobutamine infusion. Contractility was calculated by the slope of the end-systolic pressure-volume relation (ESPVR). An increase in ESPVR during dobutamine infusion was considered to indicate contractile reserve as a marker for latent RV dysfunction. The median ESPVR significantly increased from 0.32 mmHg/ml (0.13-0.72 mmHg/ml) at baseline to 0.57 mmHg/ml (0.24-1.55 mmHg/ml) during dobutamine infusion (p = 0.005). However, for five patients, no relevant increase in contractility was found, indicating impaired RV contractile reserve. There was only a weak inverse correlation between impaired contractile reserve and BNP (r = -0.28). Even asymptomatic patients with only a mildly enlarged right ventricle can have impaired RV function. Early RV dysfunction cannot be predicted accurately with BNP. PMID- 19475444 TI - Seasonal depth-related gradients in virioplankton: standing stock and relationships with microbial communities in Lake Pavin (France). AB - This study presents a depth-related survey of virioplankton abundance in Lake Pavin (Massif Central, France), in relation to the abundances of heterotrophic prokaryotes, picocyanobacteria (Pcy), autotrophic picoeukaryotes (Peu), and of autotrophic (ANF) and heterotrophic (HNF) nanoflagellates. The sampling strategy was designed to be representative of the physico-chemical gradients of the whole water column of the lake, and the seasonal variability as well. In mixolimnic surface waters, all communities were present and viral abundance peaked in summer and autumn. Viral abundance was significantly correlated (p < 0.001) with Pcy, Peu, and ANF, indicating that cyanophages and perhaps other phytoplankton viruses represent a significant pool of viral standing stocks in the mixolimnion of Lake Pavin. Microautotrophs were absent in the deep monimolimnic water masses, where viruses and heterotrophic prokaryotes exhibited highest seasonal abundances in summer and/or autumn and were significantly correlated (p < 0.001) to each other. This indicates that the anoxic monimolimnion of Lake Pavin is an exclusive habitat for viruses and heterotrophic prokaryotes. We conclude that in this habitat, host availability is prevalent over other factors (temperature, oxygen, nutrients, grazers) in favoring viral proliferation. PMID- 19475445 TI - Horizontal transfer of the tetracycline resistance gene tetM mediated by pCF10 among Enterococcus faecalis in the house fly (Musca domestica L.) alimentary canal. AB - The house fly (Musca domestica L.) alimentary canal was evaluated for the potential of horizontal transfer of tetM on plasmid pCF10 among Enterococcus faecalis. Two sets of experiments were conducted: (1) house flies without surface sterilization and (2) surface-sterilized flies. Both sets of flies were exposed to E. faecalis OG1RF:pCF10 as donor for 12 h and then E. faecalis OG1SSp as recipient for 1 h. Another group of flies received the recipient first for 12 h followed by exposure to the donor strain for 1 h. House flies were screened daily to determine the donor, recipient, and transconjugant bacterial load for up to 5 days. In addition, the sponge-like mouth parts used for food uptake (labellum) of surface-sterilized house flies were removed and analyzed for donors, recipients, and transconjugants, separately. In both groups of flies (n = 90 flies/group), transfer occurred within 24 h after exposure with a transconjugant/donor rate from 8.6 x 10(-5) to 4.5 x 10(1). Transconjugants were also isolated from the house fly labellum. Our data suggest that the house fly digestive tract provides a suitable environment for horizontal transfer of conjugative plasmids and antibiotic resistance genes among enterococci. Our results emphasize the importance of this insect as a potential vector of antibiotic-resistant bacterial strains. PMID- 19475447 TI - Inhibitory and resistance-modifying potential of plant-based alkaloids against methicillin-resistant Staphylococcus aureus (MRSA). AB - Increased prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat to the health sector worldwide due to their virulence, limited therapeutic options and their distribution in both hospital and community settings. Discovery and development of new anti-MRSA agents as alternatives to the very few antibiotics left in the armamentarium are, thus, urgently required. Recently, an efflux mechanism in MRSA has been identified as one of the main contributors of resistance towards various structurally unrelated antibiotics. The potential of reserpine (a phytoalkaloid) as efflux pump inhibitor (EPI) against various microbes remains limited as the concentration needed for inhibition is toxic to humans. This study therefore aimed to evaluate 13 alkaloid compounds as potential inhibitory agents and/or potential EPIs against a panel of three MRSA isolates which not only differ in their susceptibility to vancomycin (amongst the last drugs available to treat serious MRSA infection), but also exhibited active efflux activity. Results indicated berberine's moderate inhibitiory activity against two MRSA isolates scoring a minimum inhibitory concentration (MIC) value of 125 microg/ml. Notable efflux inhibitory activity (ranging from two- to eightfold Ethidium Bromide MIC reduction) meanwhile was detected from quinine, piperine and harmaline using reserpine as the positive control. Findings from this study support the opinion that a vast number of potential phytocompounds with pharmacological potential await discovery. Therapeutic application of these compounds, however, warrants further investigation to ascertain their pharmacodynamics and safety aspects. PMID- 19475448 TI - The selectivity of milking of Dunaliella salina. AB - The process of the simultaneous production and extraction of carotenoids, milking, of Dunaliella salina was studied. We would like to know the selectivity of this process. Could all the carotenoids produced be extracted? And would it be possible to vary the profile of the produced carotenoids and, consequently, influence the type of carotenoids extracted? By using three different D. salina strains and three different stress conditions, we varied the profiles of the carotenoids produced. Between Dunaliella bardawil and D. salina 19/18, no remarkable differences were seen in the extraction profiles, although D. salina 19/18 seemed to be better extractable. D. salina 19/25 was not "milkable" at all. The milking process could only be called selective for secondary carotenoids in case gentle mixing was used. In aerated flat-panel photobioreactors, extraction was much better, but selectiveness decreased and also chlorophyll and primary carotenoids were extracted. This was possibly related to cell damage due to shear stress. PMID- 19475449 TI - Antitermitic activities of abietane-type diterpenes from Taxodium distichum cones. AB - Eight known abietane-type diterpenes were isolated from the weak acidic fraction of the n-hexane extract from cones of Taxodium distichum, one of the extant, living fossil conifers. They were identified as 6,7-dehydroroyleanone (1), taxodal (2), taxodione (3), salvinolone (4), 14-deoxycoleon U (5), 5,6 dehydrosugiol (6), sandaracopimaric acid (7), and xanthoperol (8). The structures of these compounds were determined by comparison of NMR spectral data with published data. The antitermitic (termicidal and antifeedant) activities of the compounds 1-8 against the subterranean termite, Reticulitermes speratus Kolbe, were evaluated. Compounds 1 and 3 showed potent termicidal activity, and 5 and 8 showed potent antifeedant activity. Compound 1 was found to be one of the representative bioactive compounds in the n-hexane extract of T. distichum cones. Compounds 1-8, with the exception of 7, were oxides of ferruginol (9). Therefore, the presence of various oxidation forms of the abietane-type structure reflects their various bioactivities. PMID- 19475450 TI - Involvement of CD40 targeting miR-224 and miR-486 on the progression of pancreatic ductal adenocarcinomas. AB - BACKGROUND: Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDAC) are well known. Genetic and epigenetic data were correlated with tumor biology to find specific alterations responsible for invasion and metastasis in pancreatic ductal adenocarcinomas. METHODS: A total of 16 human PDAC cell lines were used in murine orthotopic PDAC models. By means of standardized dissemination scores, local invasion and metastatic spread were assessed. mRNA and microRNA expression were studied by microarray and TaqMan low density array. Quantitative real-time-polymerase chain reaction and flow cytometry were used for expression validation. RESULTS: CD40 was detected as a relevant target gene for differentially expressed miRNAs observed in highly invasive and metastatic PDAC only. A significant overexpression (P < .05) of CD40 related miRNAs miR-224 and miR-486 was detected in highly invasive and metastatic PDAC, whereas CD40 mRNA expression was not significantly altered. Instead, CD40 protein expression at cell surfaces of these highly invasive and metastatic PDAC was significantly reduced (P < .01). CONCLUSIONS: Epigenetic alterations with upregulated CD40-targeting miR-224 and miR-486 are related to downregulated CD40 protein expression at cell surfaces in highly invasive and metastatic PDAC. Thus, miRNA-regulated CD40 expression seems to play an important role in progression of PDAC. These data suggest a diagnostic and therapeutic potential for CD40 and/or its targeting miRNAs in PDAC. PMID- 19475451 TI - Incidence, risk factors, and impact of severe neutropenia after hyperthermic intraperitoneal mitomycin C. AB - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer and are increasingly being evaluated for use in patients with carcinomatosis from colon cancer. Mitomycin C (MMC) is one of the most frequently used HIPEC agents in the management of peritoneal-based gastrointestinal malignancies. This study analyzes the incidence and risk factors for developing neutropenia following MMC-HIPEC combined with CRS. METHODS: All patients undergoing CRS and MMC-HIPEC for appendiceal cancer between January 1993 and October 2006 were retrospectively reviewed. Logistic regression was used to identify risk factors for the development of neutropenia, defined as an absolute neutrophil count (ANC) <1,000/mm(3). RESULTS: One hundred and twenty MMC-HIPEC were performed in 117 patients with appendiceal cancer. The incidence of neutropenia was 39%. Neutropenia occurred in 57.6% of female and 21.3% of male patients (p < 0.0001). Female gender and MMC dose per body surface area (BSA) were independent risk factors for neutropenia on multivariable logistic regression [odds ratio (OR) of neutropenia in females = 3.58 (95% confidence interval, CI: 1.52, 8.43); OR for 5 unit (mg/m(2)) increase in MMC dose per BSA = 3.37 (95% CI: 1.72, 6.63)]. Neutropenia did not increase the risk of mortality, postoperative infection or length of hospital stay. CONCLUSION: Neutropenia is a frequent complication associated with MMC-HIPEC. Female sex and MMC dose per BSA are independent risk factors for neutropenia. These differences must be considered in the management of patients undergoing MMC-HIPEC to minimize the toxicity of the procedure. PMID- 19475452 TI - Ablation of high-intensity focused ultrasound assisted with SonoVue on Rabbit VX2 liver tumors: sequential findings with histopathology, immunohistochemistry, and enzyme histochemistry. AB - BACKGROUND: We investigated sequential effects of HIFU ablation combined with contrast agent SonoVue by using histopathology examination, immunohistochemistry, and enzyme histochemistry. MATERIALS AND METHODS: Forty rabbits with VX2 liver tumors were subjected to HIFU ablation. Before ablation, a bolus injection of 0.2 mL SonoVue was administrated in group II (n = 20), and normal saline solution was injected in group I (n = 20). On day 0, 3, 7, and 14 after ablation, 5 animals in each group were sacrificed. The tissue in ablated zone, transient zone (within 3 mm around ablated area), and surrounding zone (beyond 3 mm around ablated area) were collected. Coagulated volume measurement, hematoxylin-eosin staining, immunohistochemistry of Ki 67, Bcl-2, CD54, and MMP-2 to determine cell proliferation and tissue repair, and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and succinic dehydrogenase (SDH) staining to evaluate tissue viability were performed. RESULTS: The coagulated volume in group II at each time point was larger than that in group I (P < .05). After day 3, hematoxylin-eosin staining demonstrated necrosis in ablated zones and increasing surrounding fibra bands in group I and group II, while increasing expression of Ki 67, Bcl-2, CD54, and MMP-2 in transient zones was detected using immunohistochemistry in both groups (P > .05). NADPH-d and SDH staining showed dramatic decrease of enzyme activities in ablated zones immediately after ablation, while residual viable tissues in ablated zones of group II were less than those of group I (P < .05). CONCLUSION: Contrast agent SonoVue enables improvement of HIFU ablation on rabbit VX2 liver tumors. PMID- 19475453 TI - On the final size of epidemics with seasonality. AB - We first study an SIR system of differential equations with periodic coefficients describing an epidemic in a seasonal environment. Unlike in a constant environment, the final epidemic size may not be an increasing function of the basic reproduction number R(0) or of the initial fraction of infected people. Moreover, large epidemics can happen even if R(0) < 1. But like in a constant environment, the final epidemic size tends to 0 when R(0) < 1 and the initial fraction of infected people tends to 0. When R(0) > 1, the final epidemic size is bigger than the fraction 1 - 1/R(0) of the initially nonimmune population. In summary, the basic reproduction number R(0) keeps its classical threshold property but many other properties are no longer true in a seasonal environment. These theoretical results should be kept in mind when analyzing data for emerging vector-borne diseases (West-Nile, dengue, chikungunya) or air-borne diseases (SARS, pandemic influenza); all these diseases being influenced by seasonality. PMID- 19475454 TI - The effect of time distribution shape on a complex epidemic model. AB - In elaborating a model of the progress of an epidemic, it is necessary to make assumptions about the distributions of latency times and infectious times. In many models, the often implicit assumption is that these times are independent and exponentially distributed. We explore the effects of altering the distribution of latency and infectious times in a complex epidemic model with regional divisions connected by a travel intensity matrix. We show a delay in spread with more realistic latency times. More realistic infectiousness times lead to faster epidemics. The effects are similar but accentuated when compared to a purely homogeneous mixing model. PMID- 19475455 TI - The evolution of conditional dispersal strategies in spatially heterogeneous habitats. AB - To understand the evolution of dispersal, we study a Lotka-Volterra reaction diffusion-advection model for two competing species in a heterogeneous environment. The two species are assumed to be identical except for their dispersal strategies: both species disperse by random diffusion and advection along environmental gradients, but with slightly different random dispersal or advection rates. Two new phenomena are found for one-dimensional habitats and monotone intrinsic growth rates: (i) If both species disperse only by random diffusion, i.e., no advection, it was well known that the slower diffuser always wins. We show that if both species have the same advection rate which is suitably large, the faster dispersal will evolve; (ii) If both species have the same random dispersal rate, it was known that the species with a little advection along the resource gradient always wins, provided that the other species is a pure random disperser and the habitat is convex. We show that if both species have the same random dispersal rate and both also have suitably large advection rates, the species with a little smaller advection rate always wins. Implications of these results for the habitat choices of species will be discussed. Some future directions and open problems will be addressed. PMID- 19475456 TI - Modeling HIV/AIDS and tuberculosis coinfection. AB - An HIV/AIDS and TB coinfection model which considers antiretroviral therapy for the AIDS cases and treatment of all forms of TB, i.e., latent and active forms of TB, is presented. We begin by presenting an HIV/AIDS-TB coinfection model and analyze the TB and HIV/AIDS submodels separately without any intervention strategy. The TB-only model is shown to exhibit backward bifurcation when its corresponding reproduction number is less than unity. On the other hand, the HIV/AIDS-only model has a globally asymptotically stable disease-free equilibrium when its corresponding reproduction number is less than unity. We proceed to analyze the full HIV-TB coinfection model and extend the model to incorporate antiretroviral therapy for the AIDS cases and treatment of active and latent forms of TB. The thresholds and equilibria quantities for the models are determined and stabilities analyzed. From the study we conclude that treatment of AIDS cases results in a significant reductions of numbers of individuals progressing to active TB. Further, treatment of latent and active forms of TB results in delayed onset of the AIDS stage of HIV infection. PMID- 19475457 TI - Intraosseous vascularity of the distal radius: anatomy and clinical implications in distal radius fractures. AB - This study aimed to describe the intraosseous blood supply of the distal radius and its clinical implications in distal radius fractures. Twelve adult wrists from fresh cadavers (six males, six females, 50-90 years of age, mean 68 years) were injected through the brachial artery with latex. Dissections were performed using magnifying loupes and hands were processed using the Spalteholz technique. The distal radius was supplied by three main vascular systems: epiphyseal, metaphyseal, and diaphyseal. The palmar epiphyseal vessels branched from the radial artery, palmar carpal arch, and anterior branch of the anterior interosseous artery. These vessels entered the bone through the radial styloid process at level of the Lister's tubercle but palmar and sigmoid notch. The dorsal contribution to Lister's tubercle is to the dorsal epiphyseal vessels. The intraosseous point of entry to the dorsal epiphyseal vessels was from the fourth and fifth extensor compartment arteries. In the metaphyseal area, we found numerous periosteal and cortical branches originating deep in the pronator quadratus and the anterior interosseous artery. These branches provided the main supply to the distal radius. Vessels perforated the bone and formed an anastomotic network. In the diaphyseal area, only the nutrient vessel provided intraosseous vascularity in the distal radius. Numerous metaphyseal-epiphyseal branches arise within the pronator quadratus and the anterior interosseous artery and course towards the distal radius. These branches may be fundamental to the healing of the distal radius fractures and make nonunion a rare complication. PMID- 19475458 TI - Alternative approaches to ambulatory training: internal medicine residents' and program directors' perspectives. AB - BACKGROUND: Internal medicine ambulatory training redesign, including recommendations to increase ambulatory training, is a focus of national discussion. Residents' and program directors' perceptions about ambulatory training models are unknown. OBJECTIVE: To describe internal medicine residents' and program directors' perceptions regarding ambulatory training duration, alternative ambulatory training models, and factors important for ambulatory education. DESIGN: National cohort study. PARTICIPANTS: Internal medicine residents (N = 14,941) and program directors (N = 222) who completed the 2007 Internal Medicine In-Training Examination (IM-ITE) Residents Questionnaire or Program Directors Survey, representing 389 US residency programs. RESULTS: A total of 58.4% of program directors and 43.7% of residents preferred one-third or more training time in outpatient settings. Resident preferences for one-third or more outpatient training increased with higher levels of training (48.3% PGY3), female sex (52.7%), primary care program enrollment (64.8%), and anticipated outpatient-focused career, such as geriatrics. Most program directors (77.3%) and residents (58.4%) preferred training models containing weekly clinic. Although residents and program directors reported problems with competing inpatient outpatient responsibilities (74.9% and 88.1%, respectively) and felt that absence of conflict with inpatient responsibilities is important for good outpatient training (69.4% and 74.2%, respectively), only 41.6% of residents and 22.7% of program directors supported models eliminating ambulatory sessions during inpatient rotations. CONCLUSIONS: Residents' and program directors' preferences for outpatient training differ from recommendations for increased ambulatory training. Discordance was observed between reported problems with conflicting inpatient-outpatient responsibilities and preferences for models maintaining longitudinal clinic during inpatient rotations. Further study regarding benefits and barriers of ambulatory redesign is needed. PMID- 19475459 TI - Reducing the prescribing of heavily marketed medications: a randomized controlled trial. AB - CONTEXT: Prescription drug costs are a major component of health care expenditures, yet resources to support evidence-based prescribing are not widely available. OBJECTIVE: To evaluate the effectiveness of computerized prescribing alerts, with or without physician-led group educational sessions, to reduce the prescribing of heavily marketed hypnotic medications. DESIGN: Cluster-randomized controlled trial. SETTING: We randomly allocated 14 internal medicine practice sites to receive usual care, computerized prescribing alerts alone, or alerts plus group educational sessions. MEASUREMENTS: Proportion of heavily marketed hypnotics prescribed before and after the implementation of computerized alerts and educational sessions. MAIN RESULTS: The activation of computerized alerts held the prescribing of heavily marketed hypnotic medications at pre-intervention levels in both the alert-only group (adjusted risk ratio [RR] 0.97; 95% CI 0.82 1.14) and the alert-plus-education group (RR 0.98; 95% CI 0.83-1.17) while the usual-care group experienced an increase in prescribing (RR 1.31; 95% CI 1.08 1.60). Compared to the usual-care group, the relative risk of prescribing heavily marketed medications was less in both the alert-group (Ratio of risk ratios [RRR] 0.74; 95% CI 0.57-0.96) and the alert-plus-education group (RRR 0.74; 95% CI 0.58 0.97). The prescribing of heavily marketed medications was similar in the alert group and alert-plus-education group (RRR 1.02; 95% CI 0.80-1.29). Most clinicians reported that the alerts provided useful prescribing information (88%) and did not interfere with daily workflow (70%). CONCLUSIONS: Computerized decision support is an effective tool to reduce the prescribing of heavily marketed hypnotic medications in ambulatory care settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00788346. PMID- 19475460 TI - Intraabdominal bronchogenic cyst. AB - INTRODUCTION: Bronchogenic cyst is pathology of the respiratory track. It consists of a defect during the embryological development of the tracheobronchial tree. Most common presentation is as a solid or cystic mass located in mediastinum, and it is usually diagnosed in relation to respiratory problems or recurrent infections in children. In adulthood, it is a rare pathology, and its diagnosis is usually incidental. CASE REPORT: We present a case of a patient with a paraesophageal cystic mass suggestive of intraabdominal esophageal duplication cyst but, after the histopathological examination, was discovered to be a bronchogenic cyst, something extremely rare as in most cases of subdiaphragmatic location; bronchogenic cysts appear as retroperitoneal lesions. DISCUSSION: After we review the current literature, surgical extirpation appears to be the treatment of choice due to potential complications, and laparoscopic approach is a feasibily and safe procedure for this pathology up to date. PMID- 19475461 TI - Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms. AB - INTRODUCTION: Obesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms. METHODS: Data of 1,659 patients (50% male, mean age 51 +/- 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance. RESULTS: Increasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R (2) = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p < 0.0001). Compared to patients with normal weight, obese patients are more than twice as likely to have a mechanically defective LES [OR = 2.12(1.63-2.75)]. CONCLUSION: An increase in body mass index is associated with an increase in esophageal acid exposure, whether BMI was examined as a continuous or as a categorical variable; 13% of the variation in esophageal acid exposure may be attributable to variation in BMI. PMID- 19475462 TI - Volumetric and functional recovery of the remnant liver after major liver resection with prior portal vein embolization : recovery after PVE and liver resection. AB - INTRODUCTION: Portal vein embolization is an accepted method to increase the future remnant liver preoperatively. The aim of this study was to assess the effect of preoperative portal vein embolization on liver volume and function 3 months after major liver resection. MATERIALS AND METHODS: This is a retrospective case-control study. Data were collected of patients who underwent portal vein embolization prior to (extended) right hemihepatectomy and of control patients who underwent the same type of resection without prior portal vein embolization. Liver volumes were measured by computed tomography volumetry before portal vein embolization, before liver resection, and 3 months after liver resection. Liver function was assessed by hepatobiliary scintigraphy before and 3 months after liver resection. RESULTS: Ten patients were included in the embolization group and 13 in the control group. Groups were comparable for gender, age, and number of patients with a compromised liver. The mean future remnant liver volume was 33.0 +/- 8.0% prior to portal vein embolization in the embolization group and 45.6 +/- 9.1% in the control group (p < 0.01). Prior to surgery, there were no significant differences in future remnant liver volume and function between the groups. Three months postoperatively, the mean remnant liver volume was 81.9 +/- 8.9% of the initial total liver volume in the embolization group and 79.4 +/- 11.0% in the control group (p > 0.05). Remnant liver function increased up to 88.1 +/- 17.4% and 83.3 +/- 14% respectively of the original total liver function (p > 0.05). CONCLUSION: Preoperative portal vein embolization does not negatively influence postoperative liver regeneration assessed 3 months after major liver resection. PMID- 19475463 TI - Ala54Thr polymorphism of fatty acid binding protein 2, role on insulin resistance and cardiovascular risk factors in presurgical morbid obesity patients. AB - BACKGROUND: A transition G to A at codon 54 of fatty acid binding protein 2 (FABP2) results in an amino acid substitution (ala 54 to Thr 54). This polymorphism was associated with insulin resistance in some populations. OBJECTIVE: The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters, cardiovascular risk factors, and adipocytokines in patients with presurgical morbid obesity. DESIGN: A population of 55 morbid obese patients was enrolled. An indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days of written food records, and biochemical analysis (lipid profile, adipocytokines, insulin, C-reactive protein, and lipoprotein-a) were performed. The statistical analysis was performed for the combined Ala54/Thr54 and Thr54/Thr54 as a mutant-type group and wild-type group (Ala54/Ala54). RESULTS: Twenty nine (52.7%) had the genotype Ala54/Ala54 (wild type group) and 26 (47.3%) patients had the genotype Ala54/Thr54 (24 patients, 43.7%) or Thr54/Thr54 (two patients, 3.6%; mutant-type group). Insulin (22.4 +/- 16.8 vs. 26.1 +/- 17.1 mg/dl; p = 0.04) and homeostasis model assessment (6.1 +/- 2.1 vs. 6.7 +/- 4.5; p = 0.04) levels were higher in mutant-type group than wild type group. In mutant-type group, leptin levels (134.8 +/- 83 vs. 206.5 +/- 76 ng/ml; p = 0.03) were higher than wild-type group. Moreover, adiponectin levels (80.9 +/- 39.6 vs. 23.9 +/- 13.8 ng/ml; p = 0.02) were higher in wild-type group than mutant-type group. CONCLUSION: The novel finding of this study is the association of Thr54 allele with insulin resistance, leptin, and adiponectin levels in morbidly obese patients. PMID- 19475464 TI - Surgery for nonobese type 2 diabetic patients: an interventional study with duodenal-jejunal exclusion. AB - BACKGROUND: A 24-week interventional prospective trial was performed to compare the benefits of open duodenal-jejunal exclusion surgery (GJB) with a matched control group on standard medical care. METHODS: One-hundred eighty patients were screened for the surgical approach. Twelve patients accepted to be operated and presented the full eligibility criteria for surgery that includes overweight BMI (25-29.9 kg/m2), T2DM diagnosis for less than 15 years, insulin-treated patients, no history of major complications, preserved beta-cell function, and absence of autoimmunity. A matched control group (CG) of patients whom refused surgical treatment was placed to receive standard care. Patients had age of 50 (5) years, time of diagnosis 9 years (range, 3 to 15 years), time of insulin usage 6 months (range, 3 to 48 months), fasting glucose (FG), 9.8 (2.5) mg/dL, and glycated hemoglobin (A1C) 8.90 (2.12)%. RESULTS: At 24 weeks after surgery, patients experienced greater reductions on FG (14% vs. 7% on CG), A1C (from 8.78 to 7.84 in GJB-p<0.01 and 8.93 to 8.71 in CG; p<0.05 between groups) and reductions on average daily insulin requirement (93% vs. 29%, p<0.01). Ten patients stopped insulin usage in GJB but they remain taking oral medications. No differences were observed in both groups regarding BMI, body distribution and composition, blood pressure, and lipids. CONCLUSIONS: In conclusion, duodenal-jejunal exclusion was an effective treatment for nonobese T2DM subjects. GJB was superior to standard care in achieving better glycemic control along with reduction in insulin requirements. PMID- 19475465 TI - Distraction osteogenesis enhances remodeling of remote bones of the skeleton: a pilot study. AB - Bone injuries have a systemic influence on the remodeling of bone. This effect has not been examined concerning its extent and duration. We measured the systemic effect of distraction osteogenesis on the remodeling of bones of the axial skeleton by means of the mineral apposition rate and bone formation rate in an animal experiment. Distraction osteogenesis was performed on the tibiae of 24 mature Yucatan minipigs. After a 4-day latency period, the tibiae were distracted 2 mm/day for 10 days. The ensuing consolidation phase lasted 10 days. Three fluorescent labeling substances were applied intravenously: calcein green at the second postoperative day, tetracycline 1 day after the end of the distraction phase, and xylene orange 2 days before sacrifice. We prepared ground sections from the ninth right ribs. The mineral apposition rate and bone formation rate were measured histomorphometrically on labeled osteons. The median mineral apposition rate during distraction was 2.39 microm/day (2.12-2.62 microm/day), which was higher than the rate during consolidation (median, 1.62 microm/day; 1.54-1.84 microm/day). The median bone formation rate confirmed this result and was 840.51 microm(2)/day (744.20-1148.26 microm(2)/day) during distraction and 384.25 microm(2)/day (330.84-467.71 microm(2)/day) during consolidation. Thus, a short period of distraction osteogenesis appears to have an anabolic effect on the mineral apposition rate of remote cortical bone. PMID- 19475467 TI - Cephalad migration of intrathecal clonidine in an infant undergoing bilateral herniorrhaphy. PMID- 19475466 TI - Synthetic alginate is a carrier of OP-1 for bone induction. AB - Bone morphogenetic proteins (BMPs) can induce bone formation in vivo when combined with appropriate carriers. Several materials, including animal collagens and synthetic polymers, have been evaluated as carriers for BMPs. We examined alginate, an approved biomaterial for human use, as a carrier for BMP-7. In a mouse model of ectopic bone formation, the following four carriers for recombinant human OP-1 (BMP-7) were tested: alginate crosslinked by divalent cations (DC alginate), alginate crosslinked by covalent bonds (CB alginate), Type I atelocollagen, and poly-D,L-lactic acid-polyethyleneglycol block copolymer (PLA PEG). Discs of carrier materials (5-mm diameter) containing OP-1 (3-30 microg) were implanted beneath the fascia of the back muscles in six mice per group. These discs were recovered 3 weeks after implantation and subjected to radiographic and histologic studies. Ectopic bone formation occurred in a dose dependent manner after the implantation of DC alginate, atelocollagen, and PLA PEG, but occurred only at the highest dose implanted with CB alginate. Bone formation with DC alginate/OP-1 composites was equivalent to that with atelocollagen/OP-1 composites. Our data suggest DC alginate, a material free of animal products that is already approved by the FDA and other authorities, is a safe and potent carrier for OP-1. This carrier may also be applicable to various other situations in the orthopaedic field. PMID- 19475469 TI - Review article: anatomical considerations for ultrasound guidance for regional anesthesia of the neck and upper limb. AB - PURPOSE: The purpose of this narrative review is to describe an anatomical approach for residents-in-training and anesthesiologists who are learning techniques of ultrasound-guided regional anesthesia of the neck and upper limb. SOURCES: Relevant articles relating anatomy and anatomical variation to the emerging practice of ultrasound-guided regional anesthesia for the neck and upper limb were sourced via both Medline and PubMed databases. Also, our approach to teaching ultrasound technique has developed from using anatomical resources and cadaveric workshops. This approach emphasizes precise image acquisition, a detailed knowledge of anatomy and anatomical variations, and, importantly, visual interpretation of sonographic landmarks based on pattern recognition when interpreting sonograms. PRINCIPAL FINDINGS: Typical sonographic patterns orient the examiner to nerve position, which is necessary for executing successful regional anesthesia of the neck and upper limb. Only by understanding the typical anatomical arrangement can the examiner then visually interpret any individual anatomical variation that may occur. CONCLUSION: Simple sonographic anatomical patterns can provide a strategy to correctly locate nerves when performing ultrasound-guided cervical and brachial plexus anesthesia. PMID- 19475468 TI - Bilateral infraorbital nerve blocks decrease postoperative pain but do not reduce time to discharge following outpatient nasal surgery. AB - PURPOSE: While infraorbital nerve blocks have demonstrated analgesic benefits for pediatric nasal and facial plastic surgery, no studies to date have explored the effect of this regional anesthetic technique on adult postoperative recovery. We designed this study to test the hypothesis that infraorbital nerve blocks combined with a standardized general anesthetic decrease the duration of recovery following outpatient nasal surgery. METHODS: At a tertiary care university hospital, healthy adult subjects scheduled for outpatient nasal surgery were randomly assigned to receive bilateral infraorbital injections with either 0.5% bupivacaine (Group IOB) or normal saline (Group NS) using an intraoral technique immediately following induction of general anesthesia. All subjects underwent a standardized general anesthetic regimen and were transported to the recovery room following tracheal extubation. The primary outcome was the duration of recovery (minutes) from recovery room admission until actual discharge to home. Secondary outcomes included average and worst pain scores, nausea and vomiting, and supplemental opioid requirements. RESULTS: Forty patients were enrolled. A statistically significant difference in mean [SD] recovery room duration was not observed between Groups IOB and NS (131 [61] min vs 133 [58] min, respectively; P = 0.77). Subjects in Group IOB did experience a reduction in average pain on a 0 100 mm scale (mean [95% confidence interval]) compared to Group NS (-11 [-21 to 0], P = 0.047), but no other comparison of secondary outcomes was statistically significant. CONCLUSIONS: When added to a standardized general anesthetic, bilateral IOB do not decrease actual time to discharge following outpatient nasal surgery despite a beneficial effect on postoperative pain. PMID- 19475470 TI - Case report: paradoxical ventricular septal motion in the setting of primary right ventricular myocardial failure. AB - PURPOSE: In this report, a case of right ventricular (RV) failure, hemodynamic instability, and systemic organ failure is described to highlight how paradoxical ventricular systolic septal motion (PVSM), or a rightward systolic displacement of the interventricular septum, may contribute to RV ejection. CLINICAL FEATURES: Multiple inotropic medications and vasopressors were administered to treat right heart failure and systemic hypotension in a patient following combined aortic and mitral valve replacement. In the early postoperative period, echocardiographic evaluation revealed adequate left ventricular systolic function, akinesis of the RV myocardial tissues, and PVSM. In the presence of PVSM, RV fractional area of contraction was > or =35% despite akinesis of the primary RV myocardial walls. The PVSM appeared to contribute toward RV ejection. As a result, the need for multiple inotropes was re-evaluated, in considering that end-organ dysfunction was the result of systemic hypotension and prolonged vasopressor administration. After discontinuation of phosphodiesterase inhibitors, native vascular tone returned and the need for vasopressors declined. This was followed by recovery of systemic organ function. Echocardiographic re-evaluation two years later, revealed persistent akinesis of the RV myocardial tissues and PVSM, the latter appearing to contribute toward RV ejection. CONCLUSIONS: This case highlights the importance of left to RV interactions, and how PVSM may mediate these hemodynamic interactions. PMID- 19475475 TI - Effects of erbium:yttrium-aluminum-garnet and neodymium:yttrium-aluminum-garnet laser hypersensitivity treatment parameters on the bond strength of self-etch adhesives. AB - This in vitro study evaluated the shear bond strength (SBS) of two self-etch adhesives to coronal and root dentin treated with erbium:yttrium-aluminum-garnet (Er:YAG) or neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers for dentin hypersensitivity. The coronal and root dentin surfaces of 60 extracted human cuspids were divided into three groups (n = 20): (1) control (without treatment); (2) treated with Er:YAG; (3) treated with Nd:YAG laser and a one-step (S3) or two step self-etch adhesive (SE). A nano-composite was applied and SBS tests were performed. The mean SBS values were calculated, failure modes were determined, and data were subjected to statistical analysis (P = 0.05). Control/SE exhibited higher values than did control/S3 and Nd:YAG/S3 on coronal dentin (P < 0.05). No significant differences were observed between the SE and S3 groups in root dentin (P > 0.05). Comparisons of two dentin substrates did not show any difference except control/SE (P < 0.05). The failure modes were mainly adhesive. The SBSs of self-etch adhesives to Er:YAG or Nd:YAG laser-treated surfaces were comparable with control for both coronal and root dentin. PMID- 19475476 TI - Diversification of seed arrangement induced by ovule rotation and septum formation in Leguminosae. AB - The plants of Leguminosae, which comprises 731 genera, bear monocarpellary flowers. The fruit, known as a pod, generally contains a row of seeds, and the internal structure appears to be simple. In Leguminosae, the seeds are generally arranged longitudinally along the suture of the pod but, in a few genera, namely, Cassia, Indigofera, and Senna, they are arranged transversely. Transverse seed arrangement facilitates the accommodation of a considerable number of seeds and has been considered to be established by rotation of seeds during development. We studied the development both these patterns of seed arrangement, i.e., longitudinal and transverse, in Senna and Indigofera in order to elucidate the structural changes occurring in ovaries (or pods) and determine the forces responsible for rotation of ovules (or seeds) by dissecting ovaries and pods at different developmental stages. Our results showed that at an early developmental stage the ovules were obliquely oriented or transversely arranged; later, the direction of their growth was restricted by the ovary walls or neighboring ovules, and therefore the obliquely oriented ovules rotated inward or outward. Thus, it was clarified that the processes involved in the formation of the internal structure of pods are regulated in a complex manner. PMID- 19475474 TI - Male risk factors for hip fracture-a 30-year follow-up study in 7,495 men. AB - SUMMARY: Risk factors for hip fracture were studied in 7,495 randomly selected men during 30 years; 451 men had a hip fracture. High degree of leisure-time, but not work-related, physical activity, high occupational class, and high body mass index (BMI) protected against hip fracture. Smoking, tall stature, interim stroke, and dementia increased the risk. PURPOSE: The purpose was to prospectively study risk factors for hip fracture in men. METHODS: We studied midlife determinants of future hip fractures in 7,495 randomly selected men aged 46-56 years in Gothenburg, Sweden. The subjects were investigated in 1970-1973 and followed for over 30 years. Questionnaires were used regarding lifestyle factors, psychological stress, occupational class, and previous myocardial infarction, stroke, and diabetes mellitus. Alcohol problems were assessed with the aid of registers. Using the Swedish hospital discharge register, data were collected on intercurrent stroke and dementia diagnoses and on first hip fractures (X-ray-verified). RESULTS: Four hundred fifty-one men (6%) had a hip fracture. Age, tall stature, low occupational class, tobacco smoking, alcoholic intemperance, and interim stroke or dementia were independently associated with the risk of hip fracture. There were inverse associations with leisure-time physical activity, BMI, and coffee consumption. The gradient of risk for one standard deviation of multivariable risk decreased with time since measurement yet was a good alternative to dual energy X-ray absorptiometry measurements. CONCLUSIONS: High degree of leisure-time physical activity, high occupational class, and high BMI protected against hip fracture. However, work-related physical activity was not protective. Smoking, tall stature, and interim stroke or dementia increased the risk. PMID- 19475477 TI - Standardised protocol for primate faecal analysis. AB - Macroscopic analysis of primate faeces as a way to study diet is well established, but lack of standardisation of methods may handicap comparative studies of the resulting data. Here we present a proven technique, including equipment and supplies, protocol and procedure, that yields quantitative data suitable for systematic investigation within and across primate taxa. As the problems of habituation become more obvious, the application of such indirect methods may increase in usefulness. PMID- 19475478 TI - Ameliorative effects of Vaccaria segetalis extract on osteopenia in ovariectomized rats. AB - The purpose of this study was to determine the ameliorative effects of a crude extract of Vaccaria segetalis (Neck.) Garcke (Caryophyllaceae) (VSE) on osteopenia in ovariectomized (OVX) rats over 12 weeks. Rats were divided into the sham and OVX groups. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into four groups treated with water, 17beta-estradiol (30 microg/kg, daily subcutaneous injection), or VSE (0.5 or 1.0 g/kg, daily, orally) for 6 weeks. In OVX rats, the increases of serum total cholesterol were significantly decreased by VSE or 17beta-estradiol treatment. There were decreases in bone density and calcium content, including the left femur and the fourth lumbar vertebra, when compared with the sham control rats. Treatment with 17beta-estradiol or VSE ameliorated these changes induced by OVX. In addition, ovariectomy increased urinary deoxypyridinoline (DPD) amounts (P < 0.001). The increases were suppressed by 17beta-estradiol and 0.5 or 1.0 g/kg VSE (P < 0.01, P < 0.05, P < 0.01, respectively). Our results demonstrated that VSE ameliorates ovariectomy-induced osteopenia by inhibition of bone resorption. PMID- 19475479 TI - Usefulness of immunohistochemistry for differential diagnosis between benign and malignant breast lesions. AB - Immunohistochemistry (IHC) is routinely performed during pathology practice for various breast lesions. Hormone receptor and HER2 analysis for primary breast carcinoma and cytokeratin staining for sentinel lymph nodes analysis are widely conducted. In addition to those markers, there are several situations in which certain IHC staining is valuable as an ancillary tool. This manuscript will present three useful examples of IHC for making differential diagnosis between benign and malignant lesions. Case 1 is an intraductal papilloma with solid epithelial proliferation, for which diagnosis was resolved by myoepithelial markers and high-molecular-weight cytokeratins (HMWCKs). Case 2 is a noninvasive ductal carcinoma with solid and papillary morphology. Many cases with such morphology mimic benign papillomas, but expression of neuroendocrine markers may lead to the correct diagnosis. Case 3 is a benign complex sclerosing lesion, with recognition of a pseudoinvasive process by myoepithelial markers. Although IHC results were excellent in these cases, they are effective only for limited situations. It is important to use IHC with caution, and re-evaluation of histological findings on hematoxylin and eosin stain and clinicopathological correlation of each case is essential. PMID- 19475480 TI - A single substitution in amino acid 184 of the NP protein alters the replication and pathogenicity of H5N1 avian influenza viruses in chickens. AB - Changes in the NP gene of H5N1 highly pathogenic avian influenza (HPAI) viruses have previously been shown to affect viral replication, alter host gene expression levels and affect mean death times in infected chickens. Five amino acids at positions 22, 184, 400, 406, and 423 were different between the two recombinant viruses studied. In this study, we individually mutated the five amino acids that differed and determined that the difference in virus pathogenicity after NP gene exchange was a result of an alanine to lysine change at position 184 of the NP protein. Infection with viruses containing a lysine at NP 184 induced earlier mortality in chickens, increased virus titers and nitric oxide levels in tissues, and resulted in up-regulated host immune genes, such as alpha-interferon (IFN-alpha), gamma-interferon (IFN-gamma), orthomyxovirus resistance gene 1 (Mx1), and inducible nitric oxide synthase (iNOS). This study underlines the importance of the NP in avian influenza virus replication and pathogenicity. PMID- 19475481 TI - Prevalence and type distribution of human papillomavirus in 5,000 British Columbia women--implications for vaccination. AB - BACKGROUND: Human papilloma virus (HPV) prevalence studies performed in different regions and population groups across Canada would inform public health decisions regarding implementation of anti-HPV vaccines. METHODS: A total of 8,700 liquid based specimens from 8,660 women aged 13-86 from throughout British Columbia were collected. DNA was isolated from 4,980 of these samples and assessed for HPV prevalence and type distribution. HPV was detected by PCR analysis using tagged GP5+/6+ consensus primers to amplify the L1 region of HPV; typing was done by bi directional sequencing of PCR products. RESULTS: Overall HPV prevalence was 16.8% (age adjusted 15.5%). Prevalence of high-risk HPV was 13.9, and 10.7% of samples contained HPV16. HPV prevalence was highest in the youngest group of women (<20 years). One-third of HPV positive samples contained more than one HPV type. Percentages of low-grade (LGIL) and high-grade intraepithelial lesions (HGIL) containing high-risk HPV are 52.3 and 79.4%, respectively. CONCLUSIONS: Overall HPV prevalence in this study is within the range of estimates from other studies. The prevalence of HPV16 is higher than what is found in other Canadian and international studies. HPV16 and HPV18 compose a majority of the high-risk virus in this study. Use of current HPV vaccines could considerably reduce HPV-related conditions including cervical cancer and procedures such as colposcopy. PMID- 19475482 TI - Cruciform-forming inverted repeats appear to have mediated many of the microinversions that distinguish the human and chimpanzee genomes. AB - Submicroscopic inversions have contributed significantly to the genomic divergence between humans and chimpanzees over evolutionary time. Those microinversions which are flanked by segmental duplications (SDs) are presumed to have originated via non-allelic homologous recombination between SDs arranged in inverted orientation. However, the nature of the mechanisms underlying those inversions which are not flanked by SDs remains unclear. We have investigated 35 such inversions, ranging in size from 51-nt to 22056-nt, with the goal of characterizing the DNA sequences in the breakpoint-flanking regions. Using the macaque genome as an outgroup, we determined the lineage specificity of these inversions and noted that the majority (N = 31; 89%) were associated with deletions (of length between 1-nt and 6754-nt) immediately adjacent to one or both inversion breakpoints. Overrepresentations of both direct and inverted repeats, >or= 6-nt in length and capable of non-B DNA structure formation, were noted in the vicinity of breakpoint junctions suggesting that these repeats could have contributed to double strand breakage. Inverted repeats capable of cruciform structure formation were also found to be a common feature of the inversion breakpoint-flanking regions, consistent with these inversions having originated through the resolution of Holliday junction-like cruciforms. Sequences capable of non-B DNA structure formation have previously been implicated in promoting gross deletions and translocations causing human genetic disease. We conclude that non B DNA forming sequences may also have promoted the occurrence of mutations in an evolutionary context, giving rise to at least some of the inversion/deletions which now serve to distinguish the human and chimpanzee genomes. PMID- 19475483 TI - Accuracy of bottled drinking water label content. AB - The purpose of the study was to compare the accuracy of the concentration of fluoride (F), calcium (Ca), pH, and total dissolved solids (TDS) levels mentioned on the labels of the various brands of bottled drinking water available in Riyadh, Saudi Arabia. Twenty-one different brands of locally produced non carbonated (still water) bottled drinking water were collected from the supermarkets of Riyadh. The concentration of F, Ca, TDS, and pH values were noted from the labels of the bottles. The samples were analyzed for concentrations in the laboratory using the atomic absorption spectrophotometer. The mean level of F, Ca, and pH were found as 0.86 ppm, 38.47 ppm, and 7.5, respectively, which were significantly higher than the mean concentration of these elements reported in the labels. Whereas, the mean TDS concentration was found 118.87 ppm, which was significantly lower than the mean reported on the labels. In tropical countries like Saudi Arabia, the appropriate level of F concentration in drinking water as recommended by World Health Organization (WHO) should be 0.6-0.7 ppm. Since the level of F was found to be significantly higher than the WHO recommended level, the children exposed to this level could develop objectionable fluorosis. The other findings, like pH value, concentrations of Ca, and TDS, were in the range recommended by the WHO and Saudi standard limits and therefore should have no obvious significant health implications. PMID- 19475484 TI - Evaluation of drinking quality of groundwater through multivariate techniques in urban area. AB - Groundwater is a major source of drinking water in urban areas. Because of the growing threat of debasing water quality due to urbanization and development, monitoring water quality is a prerequisite to ensure its suitability for use in drinking. But analysis of a large number of properties and parameter to parameter basis evaluation of water quality is not feasible in a regular interval. Multivariate techniques could streamline the data without much loss of information to a reasonably manageable data set. In this study, using principal component analysis, 11 relevant properties of 58 water samples were grouped into three statistical factors. Discriminant analysis identified "pH influence" as the most distinguished factor and pH, Fe, and NO3- as the most discriminating variables and could be treated as water quality indicators. These were utilized to classify the sampling sites into homogeneous clusters that reflect location wise importance of specific indicator/s for use to monitor drinking water quality in the whole study area. PMID- 19475485 TI - Wetland loss under the impact of agricultural development in the Sanjiang Plain, NE China. AB - Wetland loss has been the major environmental problem in Sanjiang Plain, NE China in recent years because of the dramatic agricultural development. We determined the spatial associations of the wetland loss rates in an 11,000-km(2) study area for two intervals of period 1 (1975-1989) and period 2 (1989-2004) spanning 30 years by using geographic information systems. The landscape of this area was simple with five categories, composed of ten types, and including three natural wetland types--open water, marsh, and wet meadow. Extensive agriculture was the principal cultivation form in terms of large size farm units in the area. Agriculture has become the principal land use category replacing natural wetlands over the 30-year period. It has changed the whole landscape of the region and the landscape pattern, causing wetland loss and fragmentation. The wetland loss rate of the area was very different between the two intervals, while wetland loss was not uniform throughout the region and was influenced by the landscape characteristics, such as topography, geomorphology, and the location of the wetlands in the watershed. Despite the remarkable land use changes, the wetlands distribution in the landscapes was similar compared to their original pattern. These results indicated that agricultural development affected the areas more than the distribution pattern of the wetlands in this region. PMID- 19475486 TI - Soil salinization in the agricultural lands of Rhodope District, northeastern Greece. AB - The objective of this study was to identify seasonal and spatial trends and soil salinization patterns in a part of Rhodope District irrigated land, northeastern Greece, located east of Vistonis Lagoon. The study area is irrigated from a coastal aquifer, where salt water intrusion occurs because of extensive groundwater withdrawals. Fourteen monitoring sites were established in harvest fields in the study area, where soil samples were collected. Electrical conductivity (ECe), pH, and ion concentrations were determined in the saturated paste extract of the soil samples in the laboratory using standard methods. A clear tendency was observed for ECe to increase from April to September, i.e., within the irrigation period, indicating the effect of saline groundwater to soil. In the last years, the change from moderately sensitive (e.g., corn) to moderately tolerant crops (e.g., cotton) in the south part of the study area indicates the impacts of soil salinity. The study proposes management methods to alleviate this problem. PMID- 19475487 TI - Assessment of the bioaccessibility of polycyclic aromatic hydrocarbons in topsoils from different urban functional areas using an in vitro gastrointestinal test. AB - Profiles of the bioaccessibility of soil polycyclic aromatic hydrocarbons (PAHs) in different urban functional areas of Xiamen City, Fujian, China were investigated. A physiologically based in vitro test was used to evaluate the bioaccessibility of total and individual PAHs. There was no obvious correlation between total concentrations of PAHs and bioaccessibility during the gastrointestinal phase for the soils from different functional areas. Results showed that the bioaccessibility variation in the gastrointestinal phase (ranging from 14.6% to 63.2%) was significantly higher than that in the gastric phase (ranging from 4.9% to 21.8%). The bioaccessibility in the gastrointestinal phase was not only determined by soil organic materials but also directly related to physical and chemical properties of individual PAHs, except for two-ring PAHs. Increasing soil organic material content or decreasing ring numbers of PAHs could result in the decrease of PAH bioaccessibility. The total PAH bioaccessibility was largely contributed by individual PAHs with relatively high molecular weight. PMID- 19475488 TI - Heavy metal concentrations in surface sediments from two regions (Saros and Gokova Gulfs) of the Eastern Aegean Sea. AB - The main goal of this study is to determine the present heavy metal pollution state in the two gulfs of the Aegean Sea; Saros and Gokova Gulfs. The surface sediments were collected from 11 and eight locations in the Saros and Gokova during May 2001, respectively. The results showed that the sediments of Saros and Gokova gulfs were polluted with Pb, Cr, Zn, Mn, and Ni and Pb, Cr, Ni, and Mn, respectively. For various metals the contamination factor (CF) has been calculated to assess the degree of pollution in sediments. The sediments were noted to be not contaminated with Hg, Cd, and Cu in all areas. Moderate contaminations were observed for Pb, Cr, and Zn in Saros Gulf. The CF was moderate and very high for Ni in the Saros and the Gokova Gulf, respectively. PMID- 19475489 TI - Phenanthrene sorption to humic acids, humin, and black carbon in sediments from typical water systems in China. AB - Humic acid (HA) and humin (HM) were extracted with 0.1 M NaOH and black carbon (BC) was isolated using a combustion method at 375 degrees C from six sediments in different areas in China and their sorption isotherms for phenanthrene (Phen) were determined. All sorption isotherms were nonlinear and fitted well with the Freundlich model. Among the SOM, HM and BC with more aromatic carbon controlled the sorption nonlinearity and capacity. Compared to HM, higher K (oc) values were observed for BC due to the combustion of organic matter and native sorbates in HM. For HAs isotherms, a positive relation was observed between the K (oc) values and aliphaticity or H/C ratios, but a negative relation was shown between the n values and polarity of HAs. HA, HM, and BC were responsible for 0.4-9.3%, 46-97%, and 65-96% of the total sorption, respectively, indicating the dominance of HM and BC fractions in overall sorption of Phen by the sediments. PMID- 19475490 TI - Cattle egret (Bubulcus ibis) and Little egret (Egretta garzetta) as monitors of mercury contamination in Shadegan Wetlands of south-western Iran. AB - Mercury concentrations in feather, liver, kidney, and muscle tissue of Little egret (n = 8) and Cattle egret (n = 3) from Shadegan Wetlands in south-western Iran were examined. Liver of Little egret had significantly higher mercury compared to Cattle egret (p < 0.05). In addition, mercury values were consistently larger in Little egret when compared to Cattle egret, but mercury levels found in feather, kidney, and muscle did not differ statistically between the two bird species (p > 0.05). The small Cattle egret sample size, however, makes it difficult to conclude that the same trend would persist had we been able to include more Cattle egrets in this study. An interesting regional comparison between mercury concentrations in the feather of Little egret chicks, from China, Hong Kong, and Pakistan, and adult Little egrets, from Shadegan wetlands, revealed higher mercury in the adult of the species, as one would expect. Conversely, feathers of adult Cattle egrets form Shadegan had less mercury than values reported for young birds of the same species from Aswan in Egypt; but our Cattle egrets had higher or similar mercury concentrations to Cattle egrets from Pakistan, New York, Delaware, Puerto Rico, Hong Kong, and Cairo in Egypt. PMID- 19475491 TI - Dealing with heterogeneous regression slopes in analysis of covariance: new methodology applied to environmental effects monitoring fish survey data. AB - Analysis of covariance (ANCOVA) is a powerful statistical method which incorporates one or more covariates into the analysis to reduce error associated with measurement. ANCOVA (modeling response as a function of fish size) is frequently used to analyze environmental effects monitoring (EEM) fish survey data. In approximately 12% of fish survey data sets taken from cycles 1 to 3 of Environment Canada's EEM database for pulp and paper mills, the standard assumption of parallel regression slopes is not met. For the first three cycles of the EEM program, these data sets were classified as indicating a mill effect, but for the most part were excluded from subsequent analyses aimed at quantifying the effect. We present two different methods for initially dealing with data sets that exhibit heterogeneous slopes so that they can be analyzed using the parallel slope model. The first method identifies data sets where heterogeneous slopes are forced by a few high-influence observations. The second approach identifies data sets where a model with heterogeneous slopes is statistically, but not practically, significant: with a high coefficient of determination for the parallel slope model. These new methodologies are applied to EEM pulp and paper data sets and about 55% of cases with heterogeneous slopes can be described by a parallel slope model. We also discuss a third method that can be used to describe mill effects when regression slopes remain heterogeneous even after applying the above two methods, enabling comparison with a critical effect size. These new methodologies could benefit the EEM program by enabling more data sets to be incorporated into meta-analyses and be used to make more equitable mill monitoring decisions in the future. PMID- 19475493 TI - Synthesis, molecular docking and biological evaluation as HDAC inhibitors of cyclopeptide mimetics by a tandem three-component reaction and intramolecular [3+2] cycloaddition. AB - Novel macrocyclic peptide mimetics have been synthesized by exploiting a three component reaction and an azide-alkyne [3 + 2] cycloaddition. The prepared compounds were screened as HDAC inhibitors allowing us to identify a new compound with promising biological activity. In order to rationalize the biological results, computational studies have also been performed. PMID- 19475492 TI - Observed consultation: confidence and accuracy of assessors. AB - Judgments made by the assessors observing consultations are widely used in the assessment of medical students. The aim of this research was to study judgment accuracy and confidence and the relationship between these. Assessors watched recordings of consultations, scoring the students on: a checklist of items; attributes of consultation; a passmark scale and lastly their confidence in this last judgment. Then they were interviewed using stimulated recall to explain their rationale for scoring and confidence. Twenty-three staff assessors watched two consultations. Assessor confidence and accuracy were least for those student performances perceived near the passmark standard. The difference between confidence and accuracy, over-confidence, was greatest at this level, although at the extremes under-confidence was found. In the interviews the assessors were aware of a variety of factors that they perceived affected their scoring and confidence. As in other contexts confidence and accuracy vary and over-confidence increases the more difficult the judgments. However, this study also demonstrated under-confidence for less difficult judgments. The perception that more information would help, may improve confidence but not necessarily accuracy, so increasing over-confidence. PMID- 19475494 TI - An improved protocol for the isolation and cultivation of embryonic mouse myocytes. AB - In vitro cultures of cardiomyocytes have proven to be a useful tool for toxicological, pharmacological, and developmental studies, as well as for the study of the cellular and molecular mechanisms responsible for proper myocyte function. One deficient area of research is that of myocyte proliferation. Cardiomyocyte proliferation dramatically diminishes soon after birth and has a very limited occurrence within the adult heart, thus limiting the use of adult cells for proliferation studies. An improved understanding of the requirements for myocyte proliferation will allow for the development of better approaches to repair damaged heart tissue. Here, we provide a protocol for the reliable isolation of embryonic mouse myocytes. These myocytes behave similarly to those in vivo, including their ability to proliferate, providing an ideal system for the study of cardiomyocyte proliferation. PMID- 19475495 TI - In vitro differentiated adipocytes from a Foxc2 reporter knock-in mouse as screening tool. AB - We have developed a generic model for in vitro high-throughput screening for agents regulating transcription of genes in the mouse genome here exemplified by Foxc2, a forkhead transcription factor involved in regulation of adipocyte metabolism. We made a Foxc2-LacZ reporter "knock-in" mouse in which one of the two Foxc2 alleles has been inactivated and replaced by a LacZ reporter gene. Mouse embryonic fibroblasts, derived from such mice, were differentiated in vitro to adipocytes and used in cell-based screens. Forskolin as well as 12-O tetradecanoylphorbol-13-acetate (TPA) increased levels of Foxc2nLacZ fusion protein. We could also demonstrate that this was paralleled by an increase in Foxc2 mRNA, transcribed from the wild type allele. This generic method offers a novel way of identifying both positive and negative upstream regulators of a gene, using high-throughput screening methodology. In a cell-based screen using such methodology we demonstrate efficacy by identifying NKH477 as a Foxc2 activating compound. PMID- 19475496 TI - Up-regulation of microRNA in bladder tumor tissue is not common. AB - MicroRNAs (miRNAs) have recently been shown to down-regulate gene expression by targeting mRNA translation and to play a critical role in tumorigenesis; how they regulate bladder tumor development, particularly in patients, is, however, poorly understood. The difference in miRNA expression in a bladder tumor compared with healthy tissue from the same patients was examined using microRNA arrays in seven patients. Here, we showed that up-regulation of miRNA was not commonly found in this limited number of patients, and four miRNAs (miR-26a, miR-29c, miR-30c, miR 30e-5p) were down-regulated as a common marker in patients with a 1-3 grade of disease. Our data suggest that instead of up-regulation of carcinogenic miRNAs, loss of regulation of these miRNA may be critical for bladder tumor development in patients. PMID- 19475498 TI - Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2. AB - Fibrotic disease is a significant cause of mortality. CCN2 (connective tissue growth factor [CTGF]), a member of the CCN family of matricellular proteins, plays a significant role in driving the fibrogenic effects of cytokines such as transforming growth factor beta (TGFbeta). It has been proposed that other members of the CCN family can either promote or antagonize the action of CCN2, depending on the context. A recent elegant study published by Bruce Riser and colleagues (Am J Pathol. 174:1725-34, 2009) illustrates that CCN3 (nov) antagonizes the fibrogenic effects of CCN2. This paper, the subject of this commentary, raises the intriguing possibility that CCN3 may be used as a novel anti-fibrotic therapy. PMID- 19475497 TI - Characterization of the largest kindred with MEN2A due to a Cys609Ser RET mutation. AB - RET codon 609 point mutations are rare and may predispose to aggressive medullary thyroid carcinoma (MTC). In a kindred with 15 carriers of the Cys609Ser RET mutation we observed no MTC before 17 years of age, no lymph node metastases before 30 years and no distant metastases before 60 years. Two patients developed pheochromocytoma and one had primary hyperparathyroidism as the first sign of the syndrome. In conclusion, at variance from what already known, in this large kindred the Cys609Ser RET mutation predispose to a scarcely aggressive, highly penetrant MTC and a low penetrance of pheochromocytoma and primary hyperparathyroidism. PMID- 19475499 TI - Isolation and fluorescence spectrum of cardiac myosin from pig heart. AB - Cardiac myosin is the most abundant and bioactive protein presented in heart tissue. In this work, a simple method was described for preparation of high purity cardiac myosin for further research. With the use of a domestic pig left ventricle as the starting tissue, this method yielded 4.5 mg myosin per gram of wet tissue with a specific activity of 0.293 U/mg. The purification factor was 4.9-fold with an activity recovery of 42.1%. In addition, the investigation of fluorescence spectrum shown that the emission intensity of cardiac myosin has a dramatic decrease under the influence of an acidic environment or at temperatures higher than 30 degrees C, which could influence the normal physiological function of cardiac myosin. PMID- 19475500 TI - The utility of genetic counseling prior to offering first trimester screening options. AB - In order to evaluate the utility of genetic counseling at the time of first trimester screening in patients with no previously identified genetic concerns, we reviewed family history data for 700 women seen for genetic counseling in Utah during 2005-2006. The mean maternal age was 35 years (Range: 16-47 years). The majority of patients seen were non-Jewish Caucasians (90.8%, 634/700). A three generation pedigree was obtained from each woman by one of two certified genetic counselors and subsequently classified as "negative" (no birth defects/genetic disorders); "positive" (birth defect or genetic condition with a minimal/low risk of recurrence; additional evaluation/genetic testing during pregnancy not indicated); or "significant" (birth defect or genetic condition with an increased risk of recurrence; additional evaluation/genetic testing during the pregnancy indicated). About 72% (501/700) of the histories were negative, 19% (134/700) were positive, and about 9% (65/700) were significant. Among patients with significant family histories, 66% (n = 43) were women less than 35 years of age. We conclude that assessing a patient's family history at the time of first trimester serum screening is a valuable resource for pregnancy management. PMID- 19475501 TI - The president's page: target response or target dose. PMID- 19475502 TI - Time series analysis of hybrid neurophysiological data and application of mutual information. AB - Multivariate time series data of which some components are continuous time series and the rest are point processes are called hybrid data. Such data sets routinely arise while working with neuroscience data, EEG and spike trains would perhaps be the most obvious example. In this paper, we discuss the modeling of a hybrid time series, with the continuous component being the physiological tremors in the distal phalanx of the middle finger, and motor unit firings in the middle finger portion of the extensor digitorum communis (EDC) muscle. We employ a model for the two components based on Auto-regressive Moving Average (ARMA) type models. Another major issue to arise in the modeling of such data is to assess the goodness of fit. We suggest a visual procedure based on mutual information towards assessing the dependence pattern of hybrid data. The goodness of fit is also verified by standard model fitting diagnostic techniques for univariate data. PMID- 19475503 TI - Dyadic and triadic behaviours in infancy as precursors to later social responsiveness in young children with autistic disorder. AB - The relationship between dyadic (eye contact and affect) and triadic (joint attention) behaviours in infancy, and social responsiveness at pre-school age, was investigated in 36 children with Autistic Disorder. Measures of eye contact and affect, and joint attention, including requesting behaviours, were obtained retrospectively via parental interviews and home videos from 0- to- 24-months of age. Concurrent measures (3-5 years) included social responsiveness to another's distress and need for help. Early dyadic behaviours observed in home videos, but not as reported by parents, were associated with later social responsiveness. Many triadic behaviours (from both parent-reports and home video) were also associated with social responsiveness at follow-up. The results are consistent with the view that early dyadic and triadic behaviours, particularly sharing attention, are important for the development of later social responsiveness. PMID- 19475504 TI - HIV risk behavior self-report reliability at different recall periods. AB - Few studies have investigated the optimal length of recall period for self-report of sex and drug-use behaviors. This meta-analysis of 28 studies examined the test retest reliability of three commonly used recall periods: 1, 3, and 6 months. All three recall periods demonstrated acceptable test-retest reliability, with the exception of recall of needle sharing behaviors and 6-months recall of some sex behaviors. For most sex behaviors, a recall period of 3 months was found to produce the most reliable data; however, 6 months was best for recalling number of sex partners. Overall, shorter periods were found to be more reliable for recall of drug-use behaviors, though the most reliable length of recall period varied for different types of drugs. Implications of the findings and future directions for research are discussed. PMID- 19475506 TI - Age-dependent increase in desmosterol restores DRM formation and membrane-related functions in cholesterol-free DHCR24(-/-) mice. Neurochemical Research (34, 1167 82). PMID- 19475507 TI - Parametric versus nonparametric transfer function estimation of cerebral autoregulation from spontaneous blood-pressure oscillations. AB - Cerebral autoregulation (CAR) is a control mechanism of the brain keeping cerebral blood flow constant albeit the arterial blood pressure varies. Impaired CAR may be associated with an increased risk of cerebral ischemic events in patients with obstructive cerebrovascular disease. Spontaneous blood pressure oscillations are analyzed using a nonparametric and two parametric transfer function estimators, i.e. the autoregressive-moving-average model with exogenous inputs or the vector-autoregressive model. Performance of the methods was compared using data from patients with unilateral stenosis or occlusion. We also analyzed reproducibility by comparing partitions of the data an with data from other patients which have been measured twice. Results show that there is no significant difference between methods (ANOVA, p > 0.27), and that CAR measurements can be performed reproducibly (Kendall's tau, p < 0.0016) by all three methods. In conclusion, CAR measurements by means of spontaneous oscillations can be obtained stably and the presented parametric approaches can serve for future online application of CAR measurement. PMID- 19475505 TI - Detection of calcium transients in embryonic stem cells and their differentiated progeny. AB - A central issue in stem cell biology is the determination of function and activity of differentiated stem cells, features that define the true phenotype of mature cell types. Commonly, physiological mechanisms are used to determine the functionality of mature cell types, including those of the nervous system. Calcium imaging provides an indirect method of determining the physiological activities of a mature cell. Camgaroos are variants of yellow fluorescent protein that act as intracellular calcium sensors in transfected cells. We expressed one version of the camgaroos, Camgaroo-2, in mouse embryonic stem (ES) cells under the control of the CAG promoter system. Under the control of this promoter, Camgaroo-2 fluorescence was ubiquitously expressed in all cell types derived from the ES cells that were tested. In response to pharmacological stimulation, the fluorescence levels in transfected cells correlated with cellular depolarization and hyperpolarization. These changes were observed in both undifferentiated ES cells as well as ES cells that had been neurally induced, including putative neurons that were differentiated from transfected ES cells. The results presented here indicate that Camgaroo-2 may be used like traditional fluorescent proteins to track cells as well as to study the functionality of stem cells and their progeny. PMID- 19475508 TI - Do state mental health plans address the New Freedom Commission's goals for children's mental health? AB - The latest initiative to address mental health needs of the nation, including those of children and youth, is the President's New Freedom Commission on Mental Health (NFC). The NFC formulated a benchmark of six goals and related recommendations toward which the U.S. should strive, including the recommendation that each state develop a comprehensive mental health plan. It is not clear, however, whether the states' developed plans address the goals established by the NFC and to what degree. This project provides a summary of 50 state mental health plans regarding children and youth in the U.S. by examining components that address each of the six NFC goals and is a test of federal leadership on a state issue. Results indicate that state mental health plans addressed the NFC goals to differing degrees with specific attention to children and youth mental health services. Overall, the NFC goal of eliminating disparities in mental health services was addressed most completely, while the NFC goal of understanding that mental health and physical health are associated was addressed least often. The information provided by this analysis represents a first step in gaining a comprehensive picture about public policies for the mental health of children, adolescents, and their families. PMID- 19475509 TI - Maternal influence on adolescent self-esteem, ethnic pride and intentions to engage in risk behavior in Latino youth. AB - This study examined the relationship between ethnic pride, self-esteem and adolescent intentions to smoke cigarettes and engage in sexual intercourse. It also explored the influence of maternal levels of ethnic pride and self-esteem as indirect predictors of adolescent risk intentions. Middle school youth were randomly selected from six schools in the Bronx, NY. A total of 1,538 adolescents and their mothers were recruited. Mothers completed self-administered questionnaires about self-esteem and ethnic pride. Adolescents completed self administered questionnaires about their intentions to engage in risk behaviors, as well as items about community connectedness, language spoken at home, self esteem and ethnic pride. Results suggest that adolescent ethnic pride had protective effects on risk intentions through the mediator of self-esteem as well as independent of it. Maternal ethnic pride was associated with adolescent ethnic pride and, in turn, risk intentions, but the effect was weak in magnitude. Speaking Spanish at home was not significantly associated with ethnic pride. Both age and gender were related to ethnic pride, with ethnic pride diminishing as adolescents became older and females having higher levels of ethnic pride than males. PMID- 19475510 TI - Analysis and influence of demographic and risk factors on difficult child behaviors. AB - This descriptive study examined the distribution of risk factors in a sample that was selected on the basis of existing potential for difficult child behaviors. We inquired into whether exposure to risk factors was distributed equally across different contexts of ethnicity, locality, and child gender. Participants included 731 mother-child dyads recruited from WIC Programs in rural, suburban, and urban localities. Cumulative risk indices were constructed using neighborhood, family, and individual risk factors. The findings generally revealed that African American children and children in urban localities were exposed to higher numbers of risk factors and cumulative risk in relation to other ethnic children and localities. On the other hand, Caucasian children expressed higher levels of vulnerabilities to risk for internalizing behaviors than did other children. The results are discussed in terms of differences in contextual specific rates of risk exposure, vulnerability, and their implications for prevention and intervention research. PMID- 19475511 TI - Relaxed bodies, emancipated minds, and dominant calm. AB - William James presented "The Gospel of Relaxation" (James in W. James, Writings 1878-1899, 1992) to the 1896 graduating class of Boston Normal School of Gymnastics and a decade later he delivered his presidential address "The Energies of Men" (James in W. James, Writings 1902-1910, 1987) to the American Philosophical Association. Both lectures focus on the body's influence on emotions and on the liberating effects of live ideas on the body's natural energies. They also reflect his use of the popular spiritual hygiene literature of his day to support his arguments. The first address draws on Hannah Whitall Smith's views on disregarding our negative emotions and on Annie Payson Call's writings, specifically her views on relaxation; the second on Horace Fletcher's writings, specifically his views on anger and worry. I use these original sources to expand on key ideas in the two addresses, i.e., the role of imitation in altering unhealthy physiological habits and the energy-releasing role of suggestive ideas. PMID- 19475512 TI - Norman Vincent Peale, Smiley Blanton and the hidden energies of the mind. AB - This article on Norman Vincent Peale and Smiley Blanton, who cofounded the American Foundation of Religion and Psychiatry in 1937, focuses on books that they wrote in the 1950s: Peale's The Power of Positive Thinking (1952) and Blanton's Love or Perish (1956). Similarities between Peale's problem-solving techniques and Milton E. Erickson's psychotherapeutic methods are demonstrated, and Blanton's indebtedness to psychoanalytic theories and methods is also shown. The Peale-Blanton collaboration suggests that pastoral counselors may legitimately employ these very different therapeutic approaches depending on the needs of the individual counselee. On the other hand, the fact that they subscribed to very different therapeutic approaches raises the question as to whether the two men shared anything in common as far as their professional work with individuals was concerned. The answer is that both believed that we humans possess an enormous reservoir of untapped energies that, when released and appropriately directed, are capable of effecting fundamental changes in an individual's life. PMID- 19475513 TI - Dermatologic issues in adult survivors of childhood cancer. AB - INTRODUCTION: Common late effects experienced by childhood cancer survivors include: thyroid disturbances, pulmonary compromise, heart failure, and secondary neoplasms. Dermatologic issues have been largely unexplored. METHODS: This descriptive study consisted of an 8 item self-reported questionnaire on dermatologic issues and the Dermatology Life Quality Index. Participants reported dermatological issues that presented anytime after their diagnosis of cancer. Over a seven month period, 166 survivors seen in a specialized program for adult survivors of childhood cancer housed within an adult cancer center received a cover letter either through the mail or in the clinic setting which explained the purpose of the study. A total of 78 survivors completed the study with an average age of 29.7 years (range 19-46) and an average time since their diagnosis of 19.2 years (range 6-46). RESULTS: Dermatological issues were reported by 59.0% of survivors and 50% saw a dermatologist at least once for these concerns. Nine survivors (11.5%) reported a skin cancer and ten (12.82%) were affected by alopecia. Additionally, 26 (33.3%) of survivors reported scars related to cancer therapy as a dermatological issue, and 99% of survivors reporting scars said they did not resolve with time. DISCUSSION/CONCLUSIONS: There are a range of dermatologic issues experienced by adult childhood cancer survivors. In our non representative sample, 50% of the survivors sought specialized care from a dermatologist for their concern. Additional research is needed to more clearly understand the extent of dermatologic issues and their impact upon quality of life in childhood cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Childhood cancer survivors may frequently seek care from primary care providers. It is important for these providers to be aware of the risks associated with cancer treatments. PMID- 19475514 TI - How word decoding skill impacts text memory: The centrality deficit and how domain knowledge can compensate. AB - We examined text memory in children with word reading deficits to determine how these difficulties impact representations of text meaning. We show that even though children with poor word decoding recall more central than peripheral information, they show a significantly bigger deficit relative to controls on central than on peripheral information. We call this the centrality deficit and argue that it is the consequence of insufficient cognitive resources for connecting ideas together due to these children's resources being diverted from comprehension to word decoding. We investigated a possible compensatory mechanism for making these connections. Because a text representation is a synthesis of text information and a reader's prior knowledge, we hypothesized that having knowledge of the passage topic might reduce or eliminate the centrality deficit. Our results support this knowledge compensation hypothesis: The centrality deficit was evident when poor readers did not have prior knowledge, but was eliminated when they did. This presents an exciting avenue to pursue for possible remediation of reading comprehension in children with word identification difficulties. PMID- 19475515 TI - Purification and characterization of a novel collagenase from Bacillus pumilus Col-J. AB - The collagenase, produced extracellular by Bacillus pumilus Col-J, was purified by ammonium sulfate precipitation followed by two gel filtrations, involving Sephadex G-100 column and Sepharose Fast Flow column. Purified collagenase has a 31.53-fold increase in specific activity of 87.33 U/mg and 7.00% recovery. The collagenase has a relative molecular weight of 58.64 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The optimal temperature for the enzyme reaction was 45 degrees C. More than 50% of the original activity still remained after 5 min of incubation at 70 degrees C or 10 min at 60 degrees C. The maximal enzyme activity of collagenase was obtained at pH 7.5, and it was stable over a pH range of 6.5-8.0. The collagenase activity was strongly inhibited by Mn(2+), Pb(2+), ethylenediamine tetraacetic acid, ethylene glycol tetraacetic acid, and beta-mercaptoethanol. However, Ca(2+) and Mg(2+) greatly increased its activity. The collagenase from B. pumilus Col-J showed highly specific activity towards the native collagen from calf skin. The K(m) and V(max) of the enzyme for collagen were 0.79 mg/mL and 129.5 U, respectively. PMID- 19475517 TI - Screening of variables influencing the clavulanic acid production by Streptomyces DAUFPE 3060 strain. AB - Clavulanic acid (CA) is a beta-lactam antibiotic, which has a potent beta lactamase inhibiting activity. The influence of five variables, namely pH (6.0, 6.4, and 6.8), temperature (28 degrees C, 30 degrees C, and 32 degrees C), agitation intensity (150, 200, and 250 rpm), glycerol concentration (5.0, 7.5, and 10 g/L) and soybean flour concentration (5.0, 12.5, and 20 g/L), on CA production by a new isolate of Streptomyces (DAUFPE 3060) was investigated in 250 mL Erlenmeyer flasks using a fractional factorial design. Temperature and soybean flour concentration were shown to be the two variables that exerted the most important effects on the production of CA at 95% confidence level. The highest CA concentration (494 mg/L) was obtained after 48 h at 150 rpm, 32 degrees C, pH 6.0, 5.0 g/L glycerol, and 20 g/L soybean flour concentrations. Under these conditions, the yields of biomass and product on consumed substrate were 0.26 g(X)/g(S) and 64.3 mg(P)/g(S), respectively. Fermentations performed in 3.0-L bench-scale fermenter allowed increasing the CA production by about 60%. PMID- 19475518 TI - The tree-edit-distance, a measure for quantifying neuronal morphology. AB - The shape of neuronal cells strongly resembles botanical trees or roots of plants. To analyze and compare these complex three-dimensional structures it is important to develop suitable methods. We review the so called tree-edit-distance known from theoretical computer science and use this distance to define dissimilarity measures for neuronal cells. This measure intrinsically respects the tree-shape. It compares only those parts of two dendritic trees that have similar position in the whole tree. Therefore it can be interpreted as a generalization of methods using vector valued measures. Moreover, we show that our new measure, together with cluster analysis, is a suitable method for analyzing three-dimensional shape of hippocampal and cortical cells. PMID- 19475519 TI - Spike train analysis toolkit: enabling wider application of information-theoretic techniques to neurophysiology. AB - Conventional methods widely available for the analysis of spike trains and related neural data include various time- and frequency-domain analyses, such as peri-event and interspike interval histograms, spectral measures, and probability distributions. Information theoretic methods are increasingly recognized as significant tools for the analysis of spike train data. However, developing robust implementations of these methods can be time-consuming, and determining applicability to neural recordings can require expertise. In order to facilitate more widespread adoption of these informative methods by the neuroscience community, we have developed the Spike Train Analysis Toolkit. STAToolkit is a software package which implements, documents, and guides application of several information-theoretic spike train analysis techniques, thus minimizing the effort needed to adopt and use them. This implementation behaves like a typical Matlab toolbox, but the underlying computations are coded in C for portability, optimized for efficiency, and interfaced with Matlab via the MEX framework. STAToolkit runs on any of three major platforms: Windows, Mac OS, and Linux. The toolkit reads input from files with an easy-to-generate text-based, platform independent format. STAToolkit, including full documentation and test cases, is freely available open source via http://neuroanalysis.org , maintained as a resource for the computational neuroscience and neuroinformatics communities. Use cases drawn from somatosensory and gustatory neurophysiology, and community use of STAToolkit, demonstrate its utility and scope. PMID- 19475520 TI - Database analysis of simulated and recorded electrophysiological datasets with PANDORA's toolbox. AB - Neuronal recordings and computer simulations produce ever growing amounts of data, impeding conventional analysis methods from keeping pace. Such large datasets can be automatically analyzed by taking advantage of the well established relational database paradigm. Raw electrophysiology data can be entered into a database by extracting its interesting characteristics (e.g., firing rate). Compared to storing the raw data directly, this database representation is several orders of magnitude higher efficient in storage space and processing time. Using two large electrophysiology recording and simulation datasets, we demonstrate that the database can be queried, transformed and analyzed. This process is relatively simple and easy to learn because it takes place entirely in Matlab, using our database analysis toolbox, PANDORA. It is capable of acquiring data from common recording and simulation platforms and exchanging data with external database engines and other analysis toolboxes, which make analysis simpler and highly interoperable. PANDORA is available to be freely used and modified because it is open-source (http://software.incf.org/software/pandora/home). PMID- 19475521 TI - Macromolecular drug delivery: basic principles and therapeutic applications. AB - Macromolecular drugs hold great promise as novel therapeutics of several major disorders, such as cancer and cardiovascular disease. However, their use is limited by lack of efficient, safe, and specific delivery strategies. Successful development of such strategies requires interdisciplinary collaborations involving researchers with expertise on e.g., polymer chemistry, cell biology, nano technology, systems biology, advanced imaging methods, and clinical medicine. This poses obvious challenges to the scientific community, but also provides opportunities for the unexpected at the interface between different disciplines. This review summarizes recent studies of macromolecular delivery that should be of interest to researchers involved in macromolecular drug synthesis as well as in vitro and in vivo drug delivery studies. PMID- 19475523 TI - [The effects of physical training on the body composition of patients with COPD]. AB - AIM: The following controlled trial was conducted to determine the positive effects of exercise on the body composition of patients suffering from COPD. METHODS: A group consisting of 23 COPD patients who regularly participated in a guided exercise programme was compared with a control group consisting of 19 COPD patients who did not exercise. The relative changes of body mass index (BMI), body cell mass in % [BCM-(%)], extra cellular mass/body cell mass index (ECM/BCM index) and phase angle (angle between sinus current and sinus voltage) after 6 months and after one year were analysed for statistical differences. The values of BMI, BCM-(%), ECM/BCM index and phase angle at the beginning of the study were compared with the results during the course of the 18 months training merely within the exercising group. The body composition of the patients was determined with the help of the bioelectric impedance analysis (BIA) using the system "Nutriguard M" produced by "Data Input". RESULTS: Significantly raised phase angle values as well as significantly increased BCM-(%) values and a decreased ECM/BCM index were found in the group of patients who exercised compared with the COPD patients who did not exercise. While there were no differences concerning the BMI value, significant increases in BCM-(%) and phase angle and a significant decrease of the ECM/BCM index could be detected within the group that had been exercising. The best values were recorded after 6 months of exercising. The differences of the group responses resulted from a worsening of the body composition in the control group rather than from improvements in the exercise group. CONCLUSION: Physical exercise can improve or at least stabilise the body composition of COPD patients and should be recommended. PMID- 19475524 TI - [Why do workers apply for disability pension although their vocational ability is maintained? - a qualitative study of patients after cardiac events]. AB - The central question of this study is why workers in the employable age group apply for disability pension although from a medical point of view their vocational ability is maintained. The aim is to identify factors in the system and of the applicant which may serve as subjective prognostic indicators for maintaining employment and for determining influences which may be of prognostic value for a pension application. Concomitantly, it is aimed to obtain guidelines for practical rehabilitation and to generate impulses for further research in this field. Within a qualitative research project 16 problem-focused interviews with patients insured by "Deutsche Rentenversicherung Nord" and treated in a cardiac rehabilitation centre in Mecklenburg-Vorpommern were undertaken. Patients with either a positive or a negative subjective prognosis concerning employment were interviewed. In addition, the interviews were followed by a questionnaire one year later. The results show differences and similarities in the motivation of patients applying for disability pension. This can be traced back to psychosocial variables, sociodemographic characteristics, moderating factors and the effects of socialisation. Physical impairment was of secondary importance to the patients' motivation to apply for disability pension. The results of the follow-up questionnaire show that an existing job significantly improves the subjective prognosis for maintaining gainful employment. The application for disability pension offers the affected individual a possibility to ensure a basic existence in the case of illness and unemployment. The identified factors may be influenced by modifying the interventions and improving medical counselling during the rehabilitation period. PMID- 19475525 TI - [Dietary supplements: watch for interactions!]. PMID- 19475526 TI - Claudin-5 protein is a new differential marker for histopathological differential diagnosis of canine hemangiosarcoma. AB - AIMS: Claudin-5 protein is an endothel-specific claudin, present in tight junctions. To evaluate its usefulness as a differential diagnostic marker of canine hemangiosarcomas, the expression of claudin-5 molecule was studied in different canine tumours of vascular origin. METHODS AND RESULTS: Ninety two canine neoplastic tissue samples obtained from necropsies and biopsy specimens were routinely processed and stained immunhistochemically for claudin-5. The neoplastic endothelial cells of canine hemangiosarcomas, hemangiomas, and lymphangiomas showed a strong membrane immunoreactivity for claudin-5, but the other investigated canine malignant and benign tumours, including fibrosarcomas, myxo-, leiomyo-, cardiac rhabdomyo-, neurofibro-, synovial-, osteo-, and chondrosarcomas, spindle cell melanomas, hemangio-pericytomas, benign fibroblast proliferations, and leiomyomas were negative for this endothelial marker. In these non-vascular canine tumours intense immunostaining was detected in the endothelial cells of the incorporated intratumoural vessels and neovasculature. The canine splenic hematomas induced by hemangiosarcomas were distinguished from splenic hematomas induced by non-neoplastic lesions by the means of claudin-5 protein. In hemangiosarcomas the percentage of positive neoplastic endothelial cells was higher, and stronger when using the claudin-5 molecule compared to CD31 and vWf. CONCLUSION: The results show that claudin-5 molecule can be used as a new differential marker, and could also be of a diagnostic value in the differential diagnosis of canine hemangiosarcomas from sarcomas of other origin with hemorrhages or increased vascularization. Claudin-5 could help to reveal neoplastic proliferation of endothelial cells causing splenic hematomas and differentiate these tumours from non-vascular neoplastic splenic lesion. The immunohistochemical detection of the claudin-5 protein had a higher sensitivity than CD31, and vWf antigen in case of canine hemangiosarcomas. PMID- 19475527 TI - The pathogenesis of chronic inflammation and malignant transformation in the human upper airways: the role of beta-defensins, eNOS, cell proliferation and apoptosis. AB - The surrounding environment contains plenty of pathogens, which represent a danger of infection. The simplest way for the pathological microorganism to enter the organism is the upper airways. Inflammation of the upper airways is among the most common and frequent diseases. This category includes nasal polyposis and chronic tonsillitis. In many cases it is associated with disorders in relation to the immune response. An inflammatory infiltration of mononuclears, eosinophils, plasma and mast cells can be found in the histological structure of the polypous as well as tonsillar mucosa. One aim of this study was to determine the expression of beta-defensins and various proteins, with a possible potential role in relation to the rise and development of those changes. Another aim was to determine the relationship between the inflammatory and malignant processes in the tonsils. The samples of nasal polyps were obtained during clinically indicated endonasal surgery from patients diagnosed with nasal polyposis (n=50). The samples of tonsils were collected during surgery from patients suffering from chronic tonsillitis (n=11) or tonsillar carcinoma (n=17). Immunohistochemical procedures for the detection of human beta-defensin 1, 2, 3 (HBD-1, 2, 3), Ki- 67, endothelial nitric oxide synthase (eNOS) and cleaved caspase 3 were performed on cryostate and paraffin sections. It was proven that HBD are secreted in fairly large amounts in cases of chronic inflammation. Their secretion during the malignant transformation is limited. This is a very probable fact that plays a role in malignant transformation in tonsillar tissue. The crucial role in the development of chronic inflammation, and maybe that of malignant transformation, is played by eNOS and its product NO molecule. eNOS and the NO molecule are involved in cell cycle regulation, in the apoptotic processes and cell proliferation, as well as in the angiogenesis and vasculogenesis. Our result confirmed that eNOS is presented in the tissues of the upper airways in both chronic inflammation and carcinomatous processes. Ki-67 and cleaved caspase 3 were used as markers of cell proliferation and apoptosis. PMID- 19475528 TI - Analysis of gene status in cervical dysplastic lesions and squamous cell carcinoma using tissue microarrays. AB - Cervical displasia are classified as CIN-I, CIN-II and CIN-III. It has been observed that in at least 60% of CIN-I and CIN-II, the pathology disappears spontaneously, while around 30% persist at 24 months, 10% progress to CIN-III and 1% develops as a SCC. The factors involved in the evolution of the pathology are not defined, although infection of HPV is a necessary condition, but not the only one. For this reason, the identification of genetic changes is an essential element for understanding the carcinogenic process. It can also serve as a helpful tool for identifying patients who may be susceptible to its evolution and treatment, from patients whose lesions could regress spontaneous and for whom periodic follow-ups would be enough. Fifty three cervical biopsies from patients with dysplasia and ISCC were included in the study. These biopsies were set into nine macroarrays. Eight genes and five proteins were examined in each samples (hTERT, PIK3CA, hTERC, MYC, CCND1, BCL2, ZNF217 and p16) by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC). The results reflected that the genetic alterations of PIK3CA, ZNF217 and CCND1 were associated with the evolution of normal tissue to CIN I, those of hTERC and ERBB with the evolution of LSIL to HSIL, those of hTERT and MYC with the evolution of CIN-II/CIN-III to ISCC, and those of BCL-2 with the inception of ISCC. With regards to proteins, the expression of MYC and CCND1 in the initial stages of the illness would help in the acquisition of the altered cellular phenotype. PMID- 19475529 TI - Expression of beta-catenin and its mechanism of delocalization in intestinal-type early gastric cancer based on mucin expression. AB - The biological characteristics of intestinal-type early gastric cancers (ICs) differ based on mucin phenotypes. Beta-catenin delocalization is a predictive marker of aggressive biological behavior (submucosal invasion and lymph node metastasis) of ICs. The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes. Therefore, in the current study, the expression and mechanisms of delocalization of beta-catenin were elucidated on the basis of mucin phenotypes in 109 cases of ICs. There was increased cytoplasmic and nuclear beta-catenin expression (delocalization) in ICs with a predominant intestinal mucin phenotype (ICIP; 46.3% [25/54 cases]) compared to ICs with a predominant gastric mucin phenotype (ICGP; 20% [11/55 cases]). There were no beta-catenin or APC mutations in ICs. APC promoter hypermethylation was present in 49 of 105 (46.7%) cases of ICs. There was a significant relationship between APC promoter hypermethylation and beta-catenin delocalization in ICs, especially in ICIPs. There was no relationship between beta-catenin delocalization and APC gene loss of heterozygosity in ICs. In conclusion, we showed that beta-catenin delocalization was more evident in ICIPs, and APC promoter hypermethylation might play a role in delocalization of beta-catenin, especially in ICIPs. PMID- 19475530 TI - Unexpected presence of the neurotrophins NGF and BDNF and the neurotrophin receptor p75 in the tendon cells of the human Achilles tendon. AB - Neurotrophins are substances that have been shown to be important in growth and remodelling phases in different types of tissue. There is no information concerning the possible occurrences of neurotrophins and their receptors in tendons. In this study, sections of both chronic painful (tendinosis) and pain free (non-tendinosis) human Achilles tendons were immunohistochemically stained with antibodies against the neurotrophins NGF and BDNF, and their receptors TrkA, TrkB and p75. There were marked immunoreactions for NGF and BDNF in the tendon cells (tenocytes) of both tendinosis and non-tendinosis specimens. The tenocytes were also reactive for the receptor p75, but not for the receptors TrkA and TrkB. In addition, p75 immunoreactions were seen in nerve fascicles and in the walls of arterioles. This is the first study to identify neurotrophins in the tenocytes of human tendon. It is clear from this study that the local cells of tendons are sources of neurotrophins. The neurotrophins may play an important role in the tendon through their interaction with the receptor p75 in the tenocytes. These interactions may regulate tropic modulatory, and apoptotic effects. In conclusion, the observations show a new concept concerning production and function of neurotrophins, namely in the tenocytes of tendons. PMID- 19475531 TI - Keratinocyte dysfunction in vitiligo epidermis: cytokine microenvironment and correlation to keratinocyte apoptosis. AB - Vitiligo is a skin disorder characterized by loss of functional melanocytes. Keratinocytes contribute to melanocyte homeostasis, and keratinocyte alteration may play a role in melanocyte dysfunction in vitiligo. In particular, the release of melanogenic mediators and the level of functioning keratinocytes may affect melanocyte dysfunction in vitiligo epidermis. Keratinocyte-derived mediators involved in pigmentation, analysed by in situ hybridization, and epidermal apoptosis, detected by TUNEL assay and electron microscopy, were evaluated in lesional and perilesional skin biopsies from 15 patients with active vitiligo and in 5 control subjects. Among the melanogenic mediators, stem cell factor (SCF) and endothelin-1 (ET-1) mRNA were significantly reduced in lesional as compared to perilesional epidermis, whereas no difference was observed in mRNA of basic fibroblastic growth factor (bFGF) and granulocyte-monocyte colony stimulating factor (GM-CSF). The expression of mRNA for tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6), two pro-inflammatory cytokines with an inhibitory effect on pigmentation, was increased in the epidermis from vitiligo biopsies, whereas their expression was practically undetectable in the skin of control subjects. Apoptotic keratinocytes were more abundant in lesional vs. perilesional skin of vitiligo patients and were absent in the epidermis of control subjects. Changes in expression of keratinocyte-derived mediators observed in the present study are consistent with their differential functions in melanocyte regulation. In particular, increased TNF-alpha could contribute to keratinocyte apoptosis, which results in reduced release of melanogenic cytokines and ultimately in melanocyte disappearance. PMID- 19475532 TI - Tissue distribution of perlecan domains III and V during embryonic and fetal human development. AB - A major component of basement membranes (BMs) is perlecan, a five-domain heparan sulphate proteoglycan. During murine embryogenesis, nearly all BMs of mesenchymal origin express perlecan, and it is believed to participate in the supramolecular assembly of BMs. However, the distribution of perlecan in human embryonic and fetal tissues is widely unknown, except for cartilage anlagen of developing extremities and the fetal spine. Clinical syndromes, caused by perlecan associated mutations or gene-defects, suggest its multifunctional involvement during human development. Here we reveal the immunohistochemistry of perlecan domains III and V during human development from gestational weeks (gw) 6 to 12 in basement membrane zones (BMZs) of the developing brain, nervous system, blood vessels, skin, lung, heart, kidney, liver, intestine and skeletal system. Interestingly, a difference in the distribution of the two perlecan domains was found in the endoneurium of ganglia. Domain III is strongly present from gw 6 onwards, while domain V shows attenuated expression at this stage and has been detected abundantly only from gw 8 onwards, possibly indicating vascularization of the endoneurium during this early stage. We found perlecan to be present particularly at those stages of human development where epithelial-mesenchymal interactions occur. PMID- 19475533 TI - Tumor stroma is the predominant uPA-, uPAR-, PAI-1-expressing tissue in human breast cancer: prognostic impact. AB - Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor PAI-1, play a key role in tumor invasion and metastasis. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. Their antigens are determined in tumor tissue extracts by standardized, quality-assured immunometric assays (ELISA). Since the late 1980s, numerous independent studies have demonstrated that patients with low levels of uPA- and PAI-1 in their primary tumor tissue have significantly better survival than patients with high levels of either factor. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is most relevant to patient outcome. This missing knowledge leads to an uncertainty concerning the management of breast cancer tissue specimens. It is unclear how much tumor stroma is allowed in one tumor tissue specimen for an adequate assessment of the patients' outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas (n=60) were separated by laser capture microdissection followed by ELISA-based determination of the uPA-, uPAR- and PAI 1-levels. In addition, we have assessed uPA-, uPAR- and PAI-1 distribution in formalin-fixed, paraffin-embedded breast cancer specimens (n=60) by immunohistochemistry. The uPA-, uPAR- and PAI-1 in tumor stroma only, tumor cells only and not separated tumor tissue did not show any significant differences in protein-levels determined by ELISA. Cox regression analysis showed that patients with high uPA-, high uPAR-, and/or high PAI-1-levels, as compared to patients with low levels of either factor, showed a significantly shorter relapse-free survival and overall survival (p=0.000001). These results suggest that a strong expression of uPA, uPAR and PAI-1 in the tumor stroma, as well as in tumor cells, have the same impact on the clinical behaviour of breast cancer. CONCLUSION: When using uPA- and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for the assessment of the patients' outcome. PMID- 19475534 TI - Immunohistopathological and neuroimaging characterization of murine orthotopic xenograft models of glioblastoma multiforme recapitulating the most salient features of human disease. AB - Tumorigenesis in human glioblastoma multiforme (GBM) is driven by several genetic abnormalities with disruption of important molecular pathways, such as p53/MDM2/p14ARF and EGFR/PTEN/Akt/mTOR. The malignant progression of human GBM is also primarily associated with a peculiar multistep pathophysiological process characterized by intratumoral ischemic necrosis (i.e. pseudopalisading necrosis) and activation of the hypoxia-inducible factor (HIF)-1alpha pathway with consequent peritumoral microvascular proliferation and infiltrative behaviour. Predictable preclinical animal models of GBM should recapitulate the main pathobiological hallmarks of the human disease. In this study we describe two murine orthotopic xenograft models using U87MG and U251 human cell lines. Ten Balb/c nude male mice were orthotopically implanted with either U87MG (5 mice) or U251 (5 mice) cell lines. Intracranial tumor growth was monitored through Magnetic Resonance Imaging (MRI). Immunohistopathological examination of the whole cranium was performed 30 days after implantation. U251 orthotopic xenografts recapitulated the salient pathobiological features described for human GBM, including invasive behaviour, wide areas of pseudopalisading necrosis, florid peripheral angiogenesis, GFAP and vimentin expression, nonfunctional p53 expression, striking active-caspase-3 and HIF-1alpha expression along pseudopalisades. U87MG orthotopic xenografts proved to be very dissimilar from human GBM, showing expansile growth, occasional necrotic foci without pseudopalisades, intratumoral lacunar pattern of angiogenesis, lack of GFAP expression, functional p53 expression and inconsistent HIF-1alpha expression. Expression of pAkt was upregulated in both models. The results obtained suggest that the U251 orthotopic model may be proposed as a predictive and reliable tool in preclinical studies since it recapitulates the most salient pathobiological features reported for human GBM. PMID- 19475535 TI - Oxidative stress, isoprostanes and hepatic fibrosis. AB - An introduction to oxidative stress enlightening the spreading of interest in lipid peroxidation in the 60's and in the identification of cytotoxic aldehydes originating from it is given. The discovery of F2-isoprostanes as specific markers of oxidative stress is described. Isoprostanes are also agonists of important biological effects. Since a relationship between oxidative stress and collagen hyperproduction has been previously suggested, and since lipid peroxidation products (aldehydes) have been proposed as possible mediators of liver fibrosis, we investigated whether collagen synthesis is induced by F2 isoprostanes, which can possess receptors for signal transduction pathways. In a rat model of carbon tetrachloride-induced hepatic fibrosis, plasma isoprostanes were markedly elevated for the entire experimental period and hepatic collagen content was also increased. Moreover, when hepatic stellate cells (HSC) isolated from normal livers were cultured up to activation and then treated with F2 isoprostanes (8-epi-PGF2alpha) in the concentration range found in the in vivo studies (10(-9) to 10(-8) M), a striking increase in DNA synthesis, in cell proliferation and in collagen synthesis was observed. F2-isoprostanes also increased the production of transforming growth factor-beta1 by U937 cells, assumed as a model of Kupffer cells or liver macrophages. The hypothesis that F2 isoprostanes generated by lipid peroxidation in hepatocytes mediate HSC proliferation and collagen hyperproduction, seen in this experimental hepatic fibrosis, was reinforced by the demonstration, by using immunoblot analysis, that isoprostane receptors identical or analogous to those for thromboxane A2 (TxA2r) are present in HSC. Immunocytochemical studies showed the major localization of TxA2r in the perinuclear site and its colocalization with alpha-smooth muscle actin. PMID- 19475536 TI - Differential role of mesangial cells and podocytes in TGF-beta-induced mesangial matrix synthesis in chronic glomerular disease. AB - Glomerulosclerosis is characterized by mesangial matrix accumulation that is mediated primarily by activation of transforming growth factor-beta (TGF-beta). Unlike podocytes, mesangial cells secrete TGF-beta in response to common in vitro fibrogenic stimuli. However, mesangial immunostaining for active TGF-beta1 in chronic glomerular disease is almost negligible, despite increased mesangial TGF beta1 mRNA expression, while podocytes covering the sclerotic glomerular segments exhibit increased TGF-beta1 protein expression. The mechanisms whereby TGF-beta is activated in the diseased glomeruli and how the activated TGF-beta leads to mesangial matrix overproduction are not clear. We provide evidence that TGF-beta secreted as latent complexes by mesangial cells is stored in the mesangial matrix, from which soluble forms of latent TGF-beta are released and localized to the podocyte surface in chronic glomerular disease. Podocyte-derived reactive oxygen species, plasmin and thrombospondin-1, particularly renin-angiotensin aldosterone system-induced oxidative stress, seem to be involved in TGF-beta activation in podocytes. We also provide evidence that the TGF-beta-induced secretion of connective tissue growth factor and vascular endothelial growth factor by podocytes acts as a paracrine regulatory mechanism on mesangial cells, which may cause mesangial matrix accumulation culminating in the development of glomerulosclerosis. Collectively, these data bring new insights into our understanding of the roles of the mesangial cells and podocytes in the TGF-beta induced mesangial matrix synthesis in chronic glomerular disease. PMID- 19475537 TI - Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. AB - We review the morphofunctional characteristics of pericytes and report our observations. After a brief historical background, we consider the following aspects of pericytes: A) Origin in embryonic vasculogenesis (mesenchymal stem cells, neurocrest and other possible sources) and in embryonic and postnatal life angiogenesis (pre-existing pericytes, fibroblast/ myofibroblasts and circulating progenitor cells). B) Location in pericytic microvasculature and in the other blood vessels (including transitional cell forms and absence in lymphatic vessels), incidence (differences depending on species, topographical location, and type and stage of vessels) and distribution (specific polarities) in blood vessels. C) Morphology (cell body, and longitudinal and circumferential cytoplasmic processes), structure (nucleus, cytoplasmic organelles and distribution of microtubules, intermediate filaments and microfilaments) and surface (caveolae system). D) Basement membrane disposition, formation, components and functions. E) Contacts with endothelial cells (ECs) (peg and socket arrangements, adherent junctions and gap junctions) and with basal membrane (adhesion plaques). F) Molecular expression (pericyte marker identification). G) Functions, such as vessel stabilization, regulation of vascular tone and maintenance of local and tissue homeostasis (contractile capacity and vessel permeability regulation), matrix protein synthesis, macrophage-like properties, immunological defense, intervention in coagulation, participation in mechanisms that regulate the quiescent and angiogenic stages of blood vessels (including the behaviour of pericytes during sprouting angiogenesis and intussuceptive vascular growth, as well as pericyte interactions with endothelium and other cells, and with extracellular matrix) and plasticity, as progenitor cells with great mesenchymal potential, originating other pericytes, fibroblast/myofibroblasts, preadipocytes, chondroblasts, osteoblasts, odontoblasts, vascular smooth muscle and myointimal cells. This mesenchymal capacity is seen in a broad section on the perivascular mesenchymal cell niche hypothesis and in the concept of pericyte and EC "marriage and divorce". H) Peculiar pericyte types, such as hepatic stellate cells (Ito cells), bone marrow reticular cells and mesangial cells. I) Involvement in pathological processes, such as repair through granulation tissue, pericyte-derived tumors, tumor angiogenesis and tumoral cell metastasis, diabetic microangiopathy, fibrosis, atherosclerosis and calcific vasculopathy, lymphedema distichiasis, chronic venous insufficiency, pulmonary hypertension, Alzheimer disease and multiple sclerosis. J) Clinical and therapeutic implications (de-stabilization of vessels or formation of a stable vasculature). PMID- 19475538 TI - Empirical vs natural weighting in random effects meta-analysis. AB - This article brings into serious question the validity of empirically based weighting in random effects meta-analysis. These methods treat sample sizes as non-random, whereas they need to be part of the random effects analysis. It will be demonstrated that empirical weighting risks substantial bias. Two alternate methods are proposed. The first estimates the arithmetic mean of the population of study effect sizes per the classical model for random effects meta-analysis. We show that anything other than an unweighted mean of study effect sizes will risk serious bias for this targeted parameter. The second method estimates a patient level effect size, something quite different from the first. To prevent inconsistent estimation for this population parameter, the study effect sizes must be weighted in proportion to their total sample sizes for the trial. The two approaches will be presented for a meta-analysis of a nasal decongestant, while at the same time will produce counter-intuitive results for the DerSimonian-Laird approach, the most popular empirically based weighted method. It is concluded that all past publications based on empirically weighted random effects meta analysis should be revisited to see if the qualitative conclusions hold up under the methods proposed herein. It is also recommended that empirically based weighted random effects meta-analysis not be used in the future, unless strong cautions about the assumptions underlying these analyses are stated, and at a minimum, some form of secondary analysis based on the principles set forth in this article be provided to supplement the primary analysis. PMID- 19475540 TI - (13)C-NMR spectra of santalol derivatives: a comparison of DFT-based calculations and database-oriented prediction techniques. AB - A systematic investigation of a series of santalol and epi-santalol derivatives by means of ab initio and density functional theory (DFT) calculations together with database-oriented prediction methods leads to a configurational reassignment within this compound class. The DFT calculations as well as the HOSE-code and neural network-based predictions allow deriving a general rule set for unambiguous assignment within this compound class. The methyl group in position 2' serves as an indication for the configuration at this stereocenter allowing easy differentiation between santalol derivatives and their diastereomers belonging to the epi-santalol series. PMID- 19475539 TI - Pharmacokinetics of sertindole and its metabolite dehydrosertindole in rats and characterization of their comparative pharmacodynamics based on in vivo D2 receptor occupancy and behavioural conditioned avoidance response. AB - The objectives of this study were to characterize the pharmacokinetics of sertindole and its active metabolite dehydrosertindole in rats and to evaluate the central modulatory and behavioural pharmacodynamics including a competitive interaction model between the compounds. Following oral administration of sertindole or dehydrosertindole, the plasma concentration-time courses were determined in conjunction with striatal dopamine D(2) receptor binding. In addition, the behavioural effects were recorded in the conditioned avoidance response (CAR) paradigm. A one-compartment model with Michaelis-Menten elimination best described the pharmacokinetics of sertindole. Formation of dehydrosertindole was incorporated into the pharmacokinetic model and exhibited first-order elimination. PK/PD modelling after administration of dehydrosertindole resulted in potency estimates of 165 and 424 ng/ml for D(2) occupancy (Kd) and CAR measurements (EC(50)), respectively. The pharmacokinetics of the parent-metabolite system was integrated into a competitive pharmacodynamic E(max) model in order to quantitate the potency of sertindole with the pharmacodynamic parameters of the metabolite taken into account. Based on this approach, effect compartment concentrations of sertindole needed to attain 50% occupancy and half-maximal effect in the CAR paradigm were 133 and 338 ng/ml, respectively. The corresponding potency-estimates obtained after conventional modelling of the sertindole data without accounting for the metabolite amounted to 102 and 345 ng/ml. Based on competitive PK/PD analysis of the parent metabolite interaction, the relative contribution of dehydrosertindole to the overall pharmacological effect after sertindole administration in rats appeared to be of minor significance. This could mainly be ascribed to the relatively low extent of bioconversion of sertindole into dehydrosertindole in this species. PMID- 19475541 TI - (1)H, (13)C and (15)N NMR spectral assignments for new triazapentalene derivatives. AB - Mesomeric heteropentalene betaines are conjugated fused polyheterocyclic structures that represent interesting intermediates for organic synthesis. Five such structures, containing at least four nitrogen atoms and various substituents, have been characterized by (1)H, (13)C and (15)N NMR. We report, apparently for the first time, nitrogen NMR data and coupling information on such systems. Inter-ring long-range correlations across five bonds with (15)N ((5)J(HN)) and up to seven bonds with (13)C ((6)J(HC) and (7)J(HC)) were observed in HSQC experiments. The incorporation of an electron-withdrawing substituent such as NO(2) was observed to cause an increase in the magnitude of the remote couplings and deshielding of nearby protons, carbons and on all nitrogen atoms of the structure, including remote ones situated on other cycles. PMID- 19475543 TI - Kinship and social bonds in female chimpanzees (Pan troglodytes). AB - A large body of theoretical and empirical research suggests that kinship influences the development and maintenance of social bonds among group-living female mammals, and that human females may be unusual in the extent to which individuals form differentiated social relationships with nonrelatives. Here we combine behavioral observations of party association, spatial proximity, grooming, and space use with extensive molecular genetic analyses to determine whether female chimpanzees form strong social bonds with unrelated individuals of the same sex. We compare our results with those obtained from male chimpanzees who live in the same community and have been shown to form strong social bonds with each other. We demonstrate that party association is as good a predictor of spatial proximity and grooming in females as it is in males, that the highest party association indices are consistently found between female dyads, that the sexes do not differ in the long-term stability of their party association patterns, and that these results cannot be explained as a by-product of the tendency of females to selectively range in particular areas of the territory. We also show that close kin (i.e. mother-daughter and sibling dyads) are very rare, indicating that the vast majority of female dyads that form strong social bonds are not closely related. Additional analyses reveal that "subgroups" of females, consisting of individuals who frequently associate with one another in similar areas of the territory, do not consist of relatives. This suggests that a passive form of kin-biased dispersal, involving the differential migration of females from neighboring communities into subgroups, was also unlikely to be occurring. These results show that, as in males, kinship plays a limited role in structuring the intrasexual social relationships of female chimpanzees. PMID- 19475544 TI - Simultaneous determination of anti-diabetes/anti-obesity drugs by LC/PDA, and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS. AB - The safety of dietary supplements is questionable as there have been occasional reports of products contaminated with illegal adulterants. The present study was carried out to develop trustworthy methodologies to screen for six anti-diabetic drugs (phenformin, rosiglitazone, glipizide, glimepiride, glybenclamide and gliclazide) and six anti-obesity drugs (ephedrine, fenfluramine, T3, T4, fluoxetine and sibutramine) in dietary supplements. A simultaneous determination method of the 12 drugs by liquid chromatography coupled with a photodiode array (LC/PDA) was established and was validated for linearity (r(2) > 0.99), precision (RSD <13.3%), recoveries (88.8-115.9%) and reproducibility. Sibutramine and its analogs, N-desmethylsibutramine, were subject to further investigation by LC/MS/MS because they were one of the major illegal adulterants. Our proposed method to monitor illegal drug adulterations in dietary supplements using LC/PDA is a simple and reliable, and therefore applicable to routine drug-adulteration screening. PMID- 19475545 TI - Qualitative and quantitative determination of seven triterpene acids in Eriobotrya japonica Lindl. by high-performance liquid chromatography with photodiode array detection and mass spectrometry. AB - INTRODUCTION: The leaves of Eriobotrya japonica are used for the treatment of diabetes mellitus, chronic bronchitis, coughs and skin diseases. No method is currently available, however, by which to assess the quality of the crude herb on the basis of the quantitative profile of the main bioactive triterpene acids present. OBJECTIVE: To develop a simple and accurate HPLC-UV (photodiode array detection) method for the simultaneous quantification of seven triterpene acids in the leaves of E. japonica. METHOD: Separations were performed on an Ultimate XB-C18 column by gradient elution using methanol:formic acid. Analytes were identified by HPLC coupled with electrospray ionisation mass spectrometry experiments. The quantitative HPLC-UV method was validated for linearity, precision, accuracy, and limits of detection and quantification. RESULTS: Calibration curves presented good linear regression (r > 0.9992) within test ranges. The precision and accuracy of the method were acceptable with overall intra-day and inter-day variations of 1.35-3.30 and 1.98-4.43%, respectively, and overall recoveries of 95.60-102.67% for the seven compounds analysed. The method was successfully applied to the quantification of seven triterpene acids in eleven samples of E. japonica collected from different provinces of China. CONCLUSION: The developed assay could be considered as a suitable quality control method for E. japonica. PMID- 19475542 TI - Neuroprotective effects of estrogen therapy for cognitive and neurobiological profiles of monkey models of menopause. AB - Many postmenopausal women question whether to start or continue hormone therapy because of recent clinical trial negative results. However, evidence from other studies of postmenopausal women, and from studies in menopausal monkeys, indicate that estrogen has neurocognitive protective effects, particularly when therapy is initiated close to the time of menopause before neural systems become increasingly compromised with age. In this review, we present studies of menopausal women and female monkeys that support the concept that estrogen therapies protect both cognitive function and neurobiological processes. PMID- 19475546 TI - Incidence and patterns of regional metastasis in early oral squamous cell cancers: feasibility of submandibular gland preservation. AB - BACKGROUND: We aimed to study the incidence of metastasis to the submandibular gland (SMG) and to establish the oncologic basis of SMG preservation in early stage cancer of the oral cavity (OSCC). METHODS: This was a retrospective study of 261 patients with OSCC treated primarily with surgery at a tertiary medical center. One hundred thirty-two early-stage (T1-2, N0) OSCCs were further analyzed. RESULTS: The mean age was 59 years with male-to-female sex ratio of 1.4:1. Two hundred sixty-one neck dissections were performed with SMG removal in 253 patients. One patient with an advanced floor of mouth cancer had obvious infiltration of the SMG. Only 2.5% (3 of 116) patients with early-stage OSCC had level I metastasis; none had SMG metastases. CONCLUSION: SMG preservation in early cancers (T1-2, N0) of the oral cavity should be feasible unless there is evidence of direct invasion of the gland or close proximity of the cancer to it. PMID- 19475547 TI - Succinimide formation at Asn 55 in the complementarity determining region of a recombinant monoclonal antibody IgG1 heavy chain. AB - We investigated the formation and stability of succinimide, an intermediate of deamidation events, in recombinant monoclonal antibodies (mAbs). During the course of an analytical development study of an IgG1 mAbs, we observed that a specific antibody population could be separated from the main product by cation exchange (CEX) chromatography. The cell-based bioassay measured a approximately 70% drop in potency for this fraction. Liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) and tandem mass spectrometry (LC-MS/MS) analyses showed that the modified CEX fraction resulted from the formation of a succinimide intermediate at Asn 55 in the complementarity determining region (CDR) of the heavy chain. Biacore assay revealed a approximately 50% decrease in ligand binding activity for the succinimide-containing Fab with respect to the native Fab. It was found that the succinimide form existed as a stable intermediate with a half-life of approximately 3 h at 37 degrees C and pH 7.6. Stress studies indicated that mildly acidic pH conditions (pH 5) favored succinimide accumulation, causing a gradual loss in potency. Hydrolysis of the succinimide resulted in a further drop in potency. The implications of the succinimide formation at Asn 55, a highly conserved residue among IgG1 (mAbs), are discussed. PMID- 19475548 TI - Squamous cell carcinoma of the nasal vestibule 1993-2002: a nationwide retrospective study from DAHANCA. AB - BACKGROUND: A retrospective nationwide study of cancer of the nasal vestibule was conducted to evaluate classification systems and prognostic factors for treatment outcome. METHODS: Patients treated between 1993 and 2002 at head and neck oncology centers in Denmark were included. RESULTS: The 5-year results were locoregional control 67%, overall survival 50%, cancer-specific survival 74%. Cancer-specific survival according to Wang classification was 83%, 63%, and 39% for T1, T2, T3, respectively (p < .000). Regarding T1 tumors, 5-year locoregional control for surgery, surgery + radiotherapy (RT), or RT was 94%, 87%, or 61%, respectively (p < .000). Fifty-four Gray in 18 fractions was found comparable with 66 Gy in 33 fractions regarding T1 tumors. CONCLUSION: This national survey is the largest series of nasal vestibule cancer ever published. Wang classification is more prognostic and easier to use than the Union Internationale Contre le Cancer 2002. Surgery or hypofractionated RT can be used for T1 lesions, whereas larger lesions should be treated with combined approach. PMID- 19475549 TI - Surgical anatomy of the external branch of the superior laryngeal nerve in Chinese adults and its clinical applications. AB - BACKGROUND: The purpose of this study was to determine the anatomic features of the external branch of the superior laryngeal nerve (EBSLN) in Chinese adults. METHODS: We analyzed the anatomic distribution of the 86 EBSLNs in 43 cadavers. RESULTS: The incidences of the EBSLN in the thyroid area were 94.2% and 91.3% on the right and left sides, respectively. In accord with the Cernea classification, type 1 was 16.2%, type2a was 39.5%, and type 2 was 38.3%. There were no significant differences between the right and the left side. The high-risk position of the EBSLN was 77.8%. CONCLUSIONS: The inferior cornu of the thyroid cartilage was a reliable landmark in identifying the external branch of superior laryngeal nerve. Racial variations between the white and the Chinese should be taken into consideration for an explanation of the differences. PMID- 19475550 TI - Exploring the link between microorganisms and oral cancer: a systematic review of the literature. AB - The majority of cases of oral cancer have been related to tobacco use and heavy alcohol consumption. However, the incidence of oral cavity carcinoma appears to be increasing in many parts of the world in a manner that it is difficult to explain with traditional risk factors alone. Meanwhile, interest in the possible relationships between microorganisms and the different stages of cancer development has been rising and numerous mechanisms by which bacteria and yeast may initiate or promote carcinogenesis are currently under investigation. In particular, a persuasive body of evidence suggests a possible etiological role involving the metabolism and production of carcinogenic products, such as acetaldehyde. Other suggested mechanisms include the induction of chronic inflammation and direct interference with eukaryotic cell cycle and signaling pathways. This review aims to summarize the known associations between microbial infection and cancer and draw attention to how they may relate to oral carcinoma. PMID- 19475552 TI - Hepatic portal venous gas after upper endoscopy in a patient with a gastrointestinal stromal tumor. PMID- 19475551 TI - Papillary microcarcinoma in comparison with larger papillary thyroid carcinoma in BRAF(V600E) mutation, clinicopathological features, and immunohistochemical findings. AB - BACKGROUND: Papillary thyroid microcarcinoma (PMC; 1 cm. RESULTS: The prevalence of extrathyroidal invasion (52.2%) and initial nodal metastasis (34.9%) in patients with PMC was surprisingly high and almost as high as that for patients with PTC (72.4% and 51.8%, respectively). The rate of recurrent or persistent disease did not differ between patients with PMC and PTC (recurrent or persistent disease, 6.1% vs 14.1%; 53.4- vs 84.2-month follow-up; n = 98 vs 647; corrected p = .112). The frequency of BRAF(V600E) mutation was similar in patients with PMC and PTC (65.6% vs 67.2%). Immunohistochemical staining showed no different expression pattern according to the tumor size. CONCLUSION: These results suggest that PMC is not an occult cancer and it can act like larger PTC. Therefore, PMC should not be underestimated in practice. PMID- 19475553 TI - Diagnosis of short rib polydactyly syndrome type IV (Beemer-Langer syndrome) with cystic hygroma: A case report. AB - Short rib polydactyly syndrome (SRPS) is a very rare congenital autosomal recessive inherited disease, classified into four subtypes. It has distinct imaging findings on prenatal sonography (US) and ancillary findings on both pre- and postnatal examinations may help classify individual cases into one of four subtypes. We report the US findings in a case of SRPS type IV (Beemer-Langer dysplasia) in a male fetus with multiple congenital anomalies, including cystic hygroma. The postnatal ultrasound, radiographic, and postmortem examinations helped to classify the SRPS as type IV. We believe this is the first documented case associating cystic hygroma and polydactyly. PMID- 19475554 TI - Detection of synchronous lung tumors in patients presenting with squamous cell carcinoma of the head and neck. AB - BACKGROUND: Screening for synchronous pulmonary tumors in patients presenting with squamous cell carcinoma of the head and neck (SCCHN) is important, because detection may alter subsequent management. METHODS: We conducted a retrospective review, comparing effectiveness of pulmonary screening using thoracic CT or chest X-ray, in 1882 patients presenting with SCCHN. RESULTS: The overall rate of synchronous pulmonary tumors was 4.3%. The number needed to scan, ie, the number of thoracic CTs required to detect 1 pulmonary tumor, is reported for recurrent primary tumors, primary disease load (T and N classification), and individual primary sites. The incidence of pulmonary metastases is related to locoregional disease load while the incidence of bronchogenic carcinoma is sporadic. CONCLUSION: Although it is possible to propose a pragmatic screening protocol for pulmonary metastases, this is not possible for bronchogenic carcinomas. Therefore, we recommend that thoracic CT is used in all cases to screen for coexistent pulmonary pathology. PMID- 19475555 TI - Cryoprotectants for freeze drying of drug nano-suspensions: effect of freezing rate. AB - Drug nanoparticles are often prepared in a liquid medium, and a drying method such as freeze drying is used to convert them to an oral solid dosage form. When the dried form is reconstituted in an aqueous system, it may be redispersed to achieve its original particle size. The redispersibility of dried nanoparticles depends on the parameters of the freeze drying process. In this study, an apparatus with a freezing rate gradient was used to systematically investigate the effect of cryoprotectants on the redispersibility of nanoparticles as a function of freezing rate. Sucrose, lactose, mannitol, and polyethylene glycol were used as cryoprotectants for a naproxen nano-suspension. A fast freezing rate and a high cryoprotectant concentration were generally favored. However, under certain conditions, a slower freezing rate resulted in better redispersibility. This is probably because slow freezing can produce a more cryo-concentrated liquid phase, and the concentrated cryoprotectant in the liquid phase can more effectively protect the nanoparticles. An irreversible aggregation map was constructed as a function of the freezing rate and the cryoprotectant concentration, and shows both the favorable and unfavorable effects of cryoprotectants. PMID- 19475556 TI - Dielectric relaxation study on tramadol monohydrate and its hydrochloride salt. AB - Dielectric relaxation measurements as well as differential scanning calorimetry and X-ray diffraction investigations were performed on tramadol monohydrate and its hydrochloride salt. Examined samples do not crystallize during cooling and in consequence they reach the glassy state. In the case of the hydrochloride tramadol we are able to monitor alpha-relaxation process despite large contribution of dc conductivity to the loss spectra. It is the first such study on the salt of the drug. Up to now the dielectric spectroscopy has been regarded as useless in measuring such kind of API (active pharmaceutical ingredient). In this paper we also made some suggestions about the nature of the secondary relaxations in the amorphous tramadol monohydrate and its salt. The knowledge about the molecular mechanisms, which govern the observed secondary relaxations seems to be the key in predicting the stability of the amorphous form of the examined API. Finally additional dissolving measurements on the amorphous and crystal tramadol hydrochloride were performed. As a result we understood that dissolution properties of the amorphous form of the considered drug are comparable to those of crystalline one. However, we have found out that amorphous tramadol hydrochloride has greater ability to form tablets than its crystalline equivalent. This finding shows that amorphous drugs can be alternative even for the freely solved pharmaceuticals such as tramadol hydrochloride, because the former one has better ability to form tablets. It implies that during tabletting of the amorphous drugs there is no need to use any excipients and chemicals improving compaction properties of the API. PMID- 19475557 TI - Interactions between human UDP-glucuronosyltransferase (UGT) 2B7 and UGT1A enzymes. AB - Glucuronidation catalyzed by UDP-glucuronosyltransferase (UGT) enzymes is an important pathway in the metabolism of drugs as well as environmental chemicals. In this study, protein-protein interactions between human UGT2B7 and UGT1As and their effects on the enzymatic activities were investigated using double expression systems in HEK293 cells (UGT2B7/UGT1A1, UGT2B7/UGT1A4, UGT2B7/UGT1A6, and UGT2B7/UGT1A9). Native-PAGE analysis clearly revealed that UGT2B7 forms homo oligomers. Furthermore, hetero-oligomers of UGT2B7 with UGT1As were observed by native-PAGE analysis. Immunoprecipitation assay revealed associations of UGT2B7 with UGT1A1, UGT1A4, UGT1A6, and UGT1A9. The thermal stability of UGT2B7 was significantly increased by the coexpressed UGT1A1, UGT1A4, UGT1A6, and UGT1A9, indicating an interaction between UGT2B7 and the UGT1As. To examine the effects of the protein-protein interactions on the enzymatic activities, kinetic analyses were performed. Coexpression of the UGT1As significantly decreased K(m) and increased V(max) of zidovudine O-glucuronidation by UGT2B7. Coexpression of UGT2B7 also affected the kinetics of estradiol 3-O-glucuronidation by UGT1A1, imipramine N-glucuronidation by UGT1A4, serotonin O-glucuronidation by UGT1A6, and propofol O-glucuronidation by UGT1A9. In conclusion, it was clearly demonstrated that human UGT2B7 interacts with UGT1A enzymes, affecting their kinetics. That such interactions might occur in human liver microsomes underscores the complexities in glucuronidations in human liver. PMID- 19475558 TI - Understanding and modulating opalescence and viscosity in a monoclonal antibody formulation. AB - Opalescence and high viscosities can pose challenges for high concentration formulation of antibodies. Both phenomena result from protein-protein intermolecular interactions that can be modulated with solution ionic strength. We studied a therapeutic monoclonal antibody (mAb) that exhibits high viscosity in solutions at low ionic strength ( approximately 20 cP at 90 mg/mL and 23 degrees C) and significant opalescence at isotonic ionic strength (approximately 100 nephelometric turbidity units at 90 mg/mL and 23 degrees C). The intermolecular interactions responsible for these effects were characterized using membrane osmometry, static light scattering, and zeta potential measurements. The net protein-protein interactions were repulsive at low ionic strength ( approximately 4 mM) and attractive at isotonic ionic strengths. The high viscosities are attributed to electroviscous forces at low ionic strength and the significant opalescence at isotonic ionic strength is correlated with attractive antibody interactions. Furthermore, there appears to be a connection to critical phenomena and it is suggested that the extent of opalescence is dependent on the proximity to the critical point. We demonstrate that by balancing the repulsive and attractive forces via intermediate ionic strengths and by increasing the mAb concentration above the apparent critical concentration both opalescence and viscosity can be simultaneously minimized. PMID- 19475561 TI - Aberrant expression of synaptic plasticity-related genes in the NF1+/- mouse hippocampus. AB - Neurofibromatosis 1 (NF1) is a common single-gene disorder that causes learning impairments in patients. Neurofibromin encoded by the NF1 causal gene regulates Ras/MAPK and cAMP signaling pathways. These signaling pathways play critical roles in controlling gene transcription during synaptic plasticity and memory formation. We hypothesized that NF1 mutations disturb the expression of genes important for memory formation. To test this hypothesis, we performed DNA microarray analysis on the hippocampus of NF1(+/-) mice, the mouse model for NF1 learning disabilities. Our results indicated that genes involved in a wide spectrum of biological processes are dysregulated in the NF1(+/-) hippocampus. Many of the NF1-affected genes play critical roles in synaptic plasticity, such as Rabs, synaptotagmins, NMDAR1, CaMKII, and CREB1. Because NF1-associated learning disabilities can be reversed by lovastatin, we also determined the effect of lovastatin treatment on genome-wide expression patterns of the NF1(+/-) hippocampus. We found that lovastatin altered the expression of a large number of genes, including those disturbed by NF1 mutations. Our results reveal a genome wide overview of the molecular abnormalities in the NF1(+/-) hippocampus and should be useful for further identifying the novel molecular pathways that cause NF1 learning deficits. PMID- 19475562 TI - Characterization of calcium signaling pathways in human preadipocytes. AB - Intracellular free Ca2+ (Ca(i)2+) is an important regulator of many cellular activities; however, Ca2+ signaling is not well studied in human preadipocytes. The purpose of the present study was to characterize Ca2+ signal pathways using a confocal scanning technique and RT-PCR. It was found that spontaneous Ca(i)2+ oscillations were observed in 12.1% preadipocytes, and number of cells with Ca2+ oscillations was increased to 47.9% by 1% fetal bovine serum. Ca(i)2+ oscillations were dependent on Ca2+ entry mainly via stored-operated Ca2+ (SOC) entry. They were suppressed by the SOC entry channel blocker La3+, the phospholipase C (PLC) inhibitor U73122, the inositol trisphosphate receptor (IP3R) blocker 2-amino-ethoxydiphenyl borate, or the sarcoplasmic/endoplasmic reticulum Ca2+ pump (SERCA) inhibitors thapsigargin and cyclopiazonic acid, but not by ryanodine. The IP3R activator thimerosal increased Ca(i)2+ oscillations. In addition, the plasma membrane Ca2+ pump (PMCA) inhibitor carboxyeosin and Na+- Ca2+ exchanger (NCX) inhibitor Ni2+ both suppressed Ca2+ oscillations. RT-PCR revealed that the mRNAs for IP3R1-3, SERCA1,2, NCX3 and PMCA1,3,4, Ca(V)1.2, and TRPC1,4,6, STIM1 and Orai1 (for SOC entry channels) were significant in human preadipocytes. The present study demonstrates that multiple Ca2+ signal pathways are present in human preadipocytes, and provides a basis for investigating how Ca2+ signals regulate biological and physiological activities of human preadipocytes. PMID- 19475564 TI - Large gradient high magnetic field affects the association of MACF1 with actin and microtubule cytoskeleton. AB - The intense inhomogeneous magnetic fields acting on the diamagnetic materials naturally present in cells can generate strong magnetic forces. We have developed a superconducting magnet platform with large gradient high magnetic field (LG HMF), which can produce three magnetic force fields of -1360, 0, and 1312 T(2)/m, and three corresponding apparent gravity levels, namely 0, 1, and 2-g for diamagnetic materials. In this study, the effects of different magnetic force fields on osteoblast-like cells (MG-63 and MC3T3-E1) viability, microtubule actin crosslinking factor 1 (MACF1) expression and its association with cytoskeleton were investigated. Results showed that cell viability increased to different degrees after exposure to 0 or 1-g conditions for 24 h, but it decreased by about 30% under 2-g conditions compared with control conditions. An increase in MACF1 expression at the RNA or protein level was observed in osteoblast-like cells under the magnetic force field of -1360 T(2)/m (0-g) relative to 1312 T(2)/m (2 g). Under control conditions, anti-MACF1 staining was scattered in the cytoplasm and partially colocalized with actin filaments (AFs) or microtubules (MTs) in the majority of osteoblast-like cells. Under 0-g conditions, MACF1 labeling was concentrated at perinuclear region and colocalization was not apparent. The patterns of anti-MACF1 labeling on MTs varied with MTs' changing under LG-HMF environment. In conclusion, LG-HMF affects osteoblast-like cell viability, MACF1 distribution, expression, and its association with cytoskeleton to some extent. PMID- 19475563 TI - Association analysis of the PIP4K2A gene on chromosome 10p12 and schizophrenia in the Irish study of high density schizophrenia families (ISHDSF) and the Irish case-control study of schizophrenia (ICCSS). AB - Molecular studies support pharmacological evidence that phosphoinositide signaling is perturbed in schizophrenia and bipolar disorder. The phosphatidylinositol-4-phosphate-5-kinase type-II alpha (PIP4K2A) gene is located on chromosome 10p12. This region has been implicated in both diseases by linkage, and PIP4K2A directly by association. Given linkage evidence in the Irish Study of High Density Schizophrenia Families (ISHDSF) to a region including 10p12, we performed an association study between genetic variants at PIP4K2A and disease. No association was detected through single-marker or haplotype analysis of the whole sample. However, stratification into families positive and negative for the ISHDSF schizophrenia high-risk haplotype (HRH) in the DTNBP1 gene and re-analysis for linkage showed reduced amplitude of the 10p12 linkage peak in the DTNBP1 HRH positive families. Association analysis of the stratified sample showed a trend toward association of PIP4K2A SNPs rs1417374 and rs1409395 with schizophrenia in the DTNBP1 HRH positive families. Despite this apparent paradox, our data may therefore suggest involvement of PIP4K2A in schizophrenia in those families for whom genetic variation in DTNBP1 appears also to be a risk factor. This trend appears to arise from under-transmission of common alleles to female cases. Follow-up association analysis in a large Irish schizophrenia case-control sample (ICCSS) showed significant association with disease of a haplotype comprising these same SNPs rs1417374-rs1409395, again more so in affected females, and in cases with negative family history of the disease. This study supports a minor role for PIP4K2A in schizophrenia etiology in the Irish population. PMID- 19475565 TI - Hepatitis B virus: the genotype E puzzle. AB - Hepatitis B virus (HBV) is highly endemic throughout sub-Saharan Africa. One of the two genotypes A and E dominates in most countries. With several subgenotypes and variants, genotype A is more diverse in Africa (4.00%) than in the rest of the world (2.96%), suggesting an African origin and a long history on the continent. Despite the African slave trade, genotype E has only sporadically been found within the Americas, indicating that this genotype was introduced only during the past 200 years into the general African population. A short history for this genotype in Africa is also supported by its conspicuously low genetic diversity (1.75%), which contrasts, however, with its excessively high HBsAg prevalence and its extensive spread throughout the vast West-African genotype E crescent. We discuss the spread and routes of transmission of genotype E and suggest that the distribution and current high prevalence levels of HBV (genotype E) in Africa are the result of the extensive use of unsafe needles, potentially solving the current African genotype E puzzle and shedding new light on the high HBV prevalence in Africa. PMID- 19475566 TI - Stepwise up-regulation of microRNA expression levels from replicating to reversible and irreversible growth arrest states in WI-38 human fibroblasts. AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse genetic expression networks through their control of mRNA stability or translation. Their role in aging mechanisms has been proposed in various model systems. In this report, the expression profiling of 462 human miRNAs in the reversible growth arrest state of quiescence, and irreversible states of replicative senescence and hydrogen peroxide-induced premature senescence, are compared to young replicating lung fibroblasts. Greater numbers of up-regulated than down-regulated miRNAs are observed when cells stop proliferating, particularly in premature senescence, somewhat less in replicative senescence, and less still in quiescence. Several altered miRNA expressions are shared by the three growth arrest states, including the up-regulation of miR-34a, -624, -638 and miR-377, and the down-regulation of miR-365 and miR-512-5p. miRNAs up-regulated in both permanent growth arrest states but not in quiescence include let-7g, miR-26a, -136, -144, -195 and miR 200b. In each of the growth arrest states, miR-34a and let-7f have the most robust up-regulation in H(2)O(2)-induced premature senescence, followed by miR 638 and miR-663 in replicative senescence, and finally, miR-331-3p and miR-595 in quiescence. Our comprehensive evaluation of miRNA target correlations with known biomarkers for replicative senescence suggests that miRNAs may repress pathways controlling not only cell cycle traverse and proliferation, but also insulin-like signaling, DNA repair and apoptosis, all of which are cellular functions deficient in senescent human fibroblasts. PMID- 19475567 TI - MARCKS regulates lamellipodia formation induced by IGF-I via association with PIP2 and beta-actin at membrane microdomains. AB - Myristoylated alanine-rich C kinase substrate (MARCKS) is considered to participate in formation of F-actin-based lamellipodia, which represents the first stage of neurite formation. However, the mechanism of how MARCKS is involved in lamellipodia formation is not precisely unknown. Using SH-SY5Y cells, we demonstrated here that MARCKS was translocated from cytosol to detergent resistant membrane microdomains, known as lipid rafts, within 30 min after insulin-like growth factor-I (IGF-I) stimulation, which was accompanied by MARCKS dephosphorylation, beta-actin accumulation in lipid rafts, and lamellipodia formation. The protein kinase C inhibitor, Ro-31-8220, and Rho-kinase inhibitors, HA1077 and Y27632, themselves decreased basal phosphorylation levels of MARCKS and coincidently elicited translocation of MARCKS to lipid rafts. On the other hand, the phosphoinositide 3-kinase inhibitor, LY294002, abolished IGF-I-induced dephosphorylation, translocation of MARCKS to lipid rafts, and lamellipodia formation. Treatment of cells with neomycin, a PIP2-masking reagent, attenuated the translocation of MARCKS to lipid rafts and the lamellipodia formation induced by IGF-I, although dephosphorylation of MARCKS was not affected. Immunocytochemical and immunoprecipitation analysis indicated that IGF-I stimulation induced the translocation of MARCKS to lipid rafts in the edge of lamellipodia and formation of the complex with PIP2. Moreover, we demonstrated that knockdown of endogenous MARCKS resulted in significant attenuation of IGF-I induced beta-actin accumulation in the lipid rafts and lamellipodia formation. These results suggest a novel role for MARCKS in lamellipodia formation induced by IGF-I via the translocation of MARCKS, association with PIP2, and accumulation of beta-actin in the membrane microdomains. PMID- 19475568 TI - Osteopontin increases migration and MMP-9 up-regulation via alphavbeta3 integrin, FAK, ERK, and NF-kappaB-dependent pathway in human chondrosarcoma cells. AB - Tumor malignancy is associated with several features such as proliferation ability and frequency of metastasis. Osteopontin (OPN), which abundantly expressed in bone matrix, is involved in cell adhesion, migration, invasion and proliferation via interaction with its receptor, that is, alphavbeta3 integrin. However, the effect of OPN on migration activity in human chondrosarcoma cells is mostly unknown. Here we found that OPN increased the migration and expression of matrix metalloproteinase (MMP)-9 in human chondrosarcoma cells (JJ012 cells). RGD peptide, alphavbeta3 monoclonal antibody and MAPK kinase (MEK) inhibitors (PD98059 and U0126) but not RAD peptide inhibited the OPN-induced increase of the migration and MMP-9 up-regulation of chondrosarcoma cells. OPN stimulation increased the phosphorylation of focal adhesion kinase (FAK), MEK and extracellular signal-regulated kinase (ERK). In addition, treatment of JJ012 cells with NF-kappaB inhibitor (PDTC) or IkappaB protease inhibitor (TPCK) inhibited OPN-induced cell migration and MMP-9 up-regulation. Stimulation of JJ012 cells with OPN also induced IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. The OPN-mediated increases in MMP-9 and kappaB luciferase activities were inhibited by RGD peptide, PD98059 or FAK and ERK2 mutant. Taken together, our results indicated that OPN enhances the migration of chondrosarcoma cells by increasing MMP-9 expression through the alphavbeta3 integrin, FAK, MEK, ERK and NF-kappaB signal transduction pathway. PMID- 19475569 TI - Pharmacogenetics of smoking cessation therapy. AB - Nicotine dependence is a major health problem, with a large amount of smoking related premature deaths and disabilities. The dependence mechanism of nicotine is especially complex and is under strong genetic influence. Smoking cessation is associated with substantial health benefits. Evidence from animal and human studies suggests that genetic polymorphisms influencing pharmacokinetics and pharmacodynamics of nicotine may have great potential for aiding smoking treatment. There are more than 30 association studies and one genome-wide association study (GWAS) between genetic polymorphisms and smoking cessation following nicotine replacement therapy (NRT) and/or bupropion therapy. However, only a few candidate genes or regions were analyzed more than twice and even these genes require additional investigations in different therapeutic schemes. There are a growing number of new pharmacologic options that have not been pharmacogenetically assessed according to published literature. In addition, molecular genetics studies are needed to assess the functional mechanisms of some putative association results. Taken together, the preliminary findings are promising but raise the need for new studies with adequate sample sizes and adjustment for several potential confounding factors frequently neglected, such as comorbidity and sociodemographic factors. The current state of the art in the field encourages an optimist view that personalized treatment approaches may become possible. However, the current scientific evidence still does not support the use of pharmacogenetic tests in routine smoking cessation therapy. PMID- 19475570 TI - The association between MIF-173 G>C polymorphism and prostate cancer in southern Chinese. AB - BACKGROUND AND OBJECTIVES: Accumulating epidemiological and molecular evidence suggests that inflammation is an important component in the etiology of PCa. Macrophage migration inhibitory factor (MIF) plays an important role in the pro- and anti-inflammatory response to infection. This study is aimed at investigating the potential association between MIF-173 G>C polymorphism, Gleason score, clinical stage, and prostate-specific antigen (PSA) value with respect to PCa incidence among the Han nationality in Southern China. METHODS: Genotyping was performed by using tetraprimer polymerase chain reaction (PCR) on 259 PCa patients and 301 cancer-free controls. RESULTS: We found that the MIF-173*C variant allele was significantly associated with an increased risk of PCa [adjusted odd ratio (OR) = 2.99, 95% confident interval (CI): 1.94-4.60] and higher Gleason scores from the PCa subjects (adjusted OR = 10.72, 95% CI: 5.35 21.49). In addition, we noted that the MIF -173*C variant allele was related to higher clinical stages and PSA values in PCa patients (adjusted OR = 15.68, 95% CI: 7.40-33.23; adjusted OR = 4.37, 95% CI: 2.41-7.92, respectively). CONCLUSION: Our data suggest that MIF-173 polymorphisms may be associated with a higher incidence of prostate cancer compared to controls, and appears to be associated with higher Gleason scores, higher clinical stages, and PSA values in those with prostate cancer. PMID- 19475572 TI - Sindbis virus as a model for studies of conformational changes in a metastable virus and the role of conformational changes in in vitro antibody neutralisation. AB - Sindbis virus has long been the prototypical alphavirus used in the study of assembly of icosahedral viruses which contain membranes. Much is known about the assembly pathway and molecular architecture of this virus, and models of mechanisms of infection and release of the viral RNA have been proposed. This review will focus on the structural aspects of in vitro antibody neutralisation of a metastable alphavirus, Sindbis virus, which results from antibody induced conformational changes. For the alphaviruses, structures of in vitro antibody induced conformational neutralisation for Sindbis virus, and receptor occlusion for Sindbis and Ross River virus (RRV) have been reported. A model is presented which could extend the mechanism of antibody induced conformational neutralisation to any metastable virus structure. PMID- 19475574 TI - Prognostic indicators of poor short-term outcome of physiotherapy intervention in women with stress urinary incontinence. AB - AIMS: To identify prognostic indicators independently associated with poor outcome of physiotherapy intervention in women with primary or recurrent stress urinary incontinence (stress UI). METHODS: A prospective cohort study was performed in physiotherapy practices in primary care to identify prognostic indicators 12 weeks after initiation of physiotherapy intervention. Patients were referred by general practitioners or urogynecologists. Risk factors for stress UI were examined as potential prognostic indicators of poor outcome. The primary outcomes were defined as poor outcome on the binary Leakage Severity scale (LS scale) and the binary global perceived effectiveness (GPE) score. RESULTS: Two hundred sixty-seven women, with a mean age of 47.7 (SD = 8.3), with stress UI for at least 6 months were included. At 12 weeks, 43% and 59% of the women were considered recovered on the binary LS scale and the binary GPE score, respectively. Prognostic indicators associated with poor outcome included 11 indicators based on the binary LS scale and 8 based on the binary GPE score. The prognostic indicators shared by both models show that poor recovery was associated with women with severe stress UI, POP-Q stage > II, poor outcome of physiotherapy intervention for a previous UI episode, prolonged second stage of labor, BMI > 30, high psychological distress, and poor physical health. CONCLUSIONS: This study provides robust evidence of clinically meaningful prognostic indicators of poor short-term outcome. These findings need to be confirmed by replication studies. PMID- 19475573 TI - Bladder neck closure and suprapubic tube placement in a debilitated patient population. AB - AIMS: Bladder neck closure (BNC) with suprapubic tube (SPT) placement is a method of bladder management for patients with neurogenic bladders (NGB). We evaluated our experience at one institution. METHODS: We conducted a retrospective chart review of patients who received BNC with SPT placement from 1999 to 2008. RESULTS: Twenty-nine patients (24 females and 5 males, average age 53.4 +/- 9.6 years) underwent BNC with SPT placement. Cause of NGB was multiple sclerosis (48%), spinal injury (28%), or myelodysplasia (17%). All but one were dependent on caregivers for activities of daily living. Preoperative urodynamics studies were performed on 23 patients. Retropubic BNC was performed in 26 of 29 patients. Two females had a transvaginal approach, and one male had a perineal approach. Early (<90 days) postoperative complication rate was 52%. Persistent urine leakage was present in eight patients: two peristomal leakage and six urethral leakage. All three non-retropubic BNC had postoperative fistulas (P = 0.01). Catheter complications were associated with seven of the eight urinary leaks (P = 0.01). CONCLUSIONS: BNC with SPT is a method of bladder management in the NGB population, particularly suited to those with a low functional status. Fistula rates are significantly higher with non-retropubic BNC (P = 0.01). Poor catheter care in the postoperative period is associated with postoperative urinary leakage (P = 0.01). PMID- 19475575 TI - Lower urinary tract symptoms following neurological illness may be influenced by multiple factors: observations from a neurorehabilitation service in a developing country. AB - AIMS: To evaluate the pattern of lower urinary tract dysfunction (LUTD) in patients with neurological disease in the setting of a rehabilitation service in a developing country, and analyze causes for unexpected lower urinary tract symptoms (LUTS). METHODS: Patients with neurological disorders and having significant LUTS were prospectively evaluated. Level of neurological lesion was localized by neurological examination and investigations. LUTD was evaluated by symptom analysis, bladder diaries and ultrasonography. Storage symptoms were managed using antimuscarinic medications and voiding dysfunction, when significant, was managed by catheterization and patients were regularly followed up. Patients with symptoms that had not been expected based upon their level of neurological lesion were further evaluated. RESULTS: Fifty patients (mean age 43.5 +/- 18.3 years) were included and according to neurological localization, were categorized into suprapontine (n = 9; 18%), infrapontine/suprasacral (n = 25; 50%) or infrasacral (n = 16; 32%) groups. Incontinence was more common in patients with suprapontine and infrapontine/suprasacral lesions (n = 20) (P < 0.03), hesitancy more common with infrapontine/suprasacral lesions (n = 20) (P = 0.004) and retention more with infrasacral lesions (n = 13) (P < 0.001). Patients belonging to suprapontine and infrapontine/suprasacral groups more likely showed improvement at follow up (P = 0.008). Fourteen patients (28%) had unexpected LUTS and this was due to urological causes (n = 6) or multiaxial neurological involvement (n = 8). Potentially treatable factors were managed, resulting in symptom relief. CONCLUSION: LUTS in neurological disease may be at variance with the pattern expected based upon level of neurological lesion. Such patients may require further evaluation and consideration should be given to concomitant urological conditions and multiaxial neurological involvement. PMID- 19475576 TI - Reductions in stress urinary incontinence episodes: what is clinically important for women? AB - AIM: To expand our understanding of the clinical importance to patients with stress urinary incontinence (SUI) of reductions in incontinence episode frequency (IEF) that fall short of a complete cure. METHODS: We used an integrated database that included data from 1,913 women with SUI who were enrolled in four randomized, placebo-controlled pharmaceutical clinical trials and examined the relationship between various levels of reduction in IEF and minimally clinical important difference (MCID) levels established for the validated Incontinence Quality of Life (I-QOL) questionnaire. The first decile of IEF reduction to exceed the within-group MCID was considered to be the point at which the reduction in IEF first became clinically important. The between-group MCID was then used to determine when further reductions in incontinence represented clinically relevant incremental improvements for patients. RESULTS: Improvements in condition-specific quality of life were not clinically important until the fifth decile of IEF reduction, representing a reduction in IEF >40% to 70% to 90% to a single nucleotide polymorphism and risk of Taiwanese PD. AB - Early onset Parkinson's disease (PD) has been associated with mutations in Parkin. We screened Parkin mutations in a cohort of Taiwanese early onset PD using direct cDNA sequencing. Two deletions (Ex2-3del and Ex5del), one point mutation (R334C), one 86-bp IVS9 insertion (c.1084intron(+)), and two polymorphisms (S167N and V380L) were identified. The mutations identified are heterozygous and none of the mutation carriers possess two Parkin mutations. The c.1084intron(+) was due to a novel IVS9 g > a change. To assess the association of IVS9 g > a, S167N and V380L with the risk of PD, we conducted a case-control study in a cohort of PD and ethnically matched controls. Although the difference is not significant, the V380L C allele frequency was notably lower in PD patients than the controls and a trend toward decrease in risk of developing PD was evident (odds ratio: 0.71, 95% confidence interval: 0.53-0.97, P = 0.029). Contrarily the IVS9 g > a a allele frequency was notably higher in PD patients than the controls and a trend toward increase in risk of developing PD was also evident (odds ratio: 1.65, 95% confidence interval: 1.06-2.59, P = 0.028). Quantitative real-time PCR showed that the relative Parkin c.1084intron(+) mRNA expression was increased in PD patients with IVS9 ga genotype as compared to gg genotype. Pairwise genotype analysis revealed that IVS9 gg genotype strengthens the negative association of the V380L GC genotype with PD (odds ratio: 0.67, 95% confidence interval: 0.48-0.94, P = 0.021). The results of Parkin mutation/polymorphism screening may contribute to our understanding of PD. PMID- 19475584 TI - Prognostic impact of lymphatic invasion in patients with node-negative gastric cancer. AB - BACKGROUND AND OBJECTIVES: This study investigated the prognostic impact of lymphatic invasion on the outcome of patients with node-negative gastric cancer. METHODS: A total of 828 patients with node-negative gastric cancer who underwent curative gastrectomy were reviewed retrospectively. The clinicopathological features and prognoses of patients with lymphatic invasion were compared to those of patients without such invasion. RESULTS: The total rate of lymphatic invasion was 18.2% in node-negative gastric cancers, with a significant difference between early gastric cancers (9.8%) and advanced gastric cancers (49.2%). The presence of lymphatic invasion correlated significantly with tumor location, size and depth of tumor (P < 0.01). Lymphatic invasion was significantly associated with a poorer overall survival in node-negative gastric cancer patients on univariate analysis (P < 0.001) as well as multivariate analysis (P < 0.01). CONCLUSIONS: Lymphatic invasion provides additional useful information that could be applied to identify patients at high risk for recurrence who might be candidates for adjuvant therapies in patients with node-negative gastric cancers. PMID- 19475585 TI - Room-temperature C-H bond activation of methane by bare [P(4)O(10)](*+). AB - No need for a metal: A combination of mass spectrometry and computational studies (density functional theory and coupled-cluster methods) shows that [P(4)O(10)](.+) is the first polynuclear nonmetal oxide cation that is capable of activating the C--H bond of methane at room temperature (see picture). This process represents a further example in the reactivity of oxygen-centered radicals. PMID- 19475583 TI - A candidate gene study of Tardive dyskinesia in the CATIE schizophrenia trial. AB - Tardive dyskinesia (TD) is a movement disorder characterized by involuntary oro facial, limb, and truncal movements. As a genetic basis for inter-individual variation is assumed, there have been a sizeable number of candidate gene studies. All subjects met diagnostic criteria for schizophrenia and were randomized to receive antipsychotic medications as participants in the Clinical Antipsychotic Trials of Intervention Effectiveness project (CATIE). TD was assessed via the Abnormal Involuntary Movement Scale at regular intervals. Probable TD was defined as meeting Schooler-Kane criteria at any scheduled CATIE visit (207/710 subjects, 29.2%). A total of 128 candidate genes were studied in 710 subjects-2,580 SNPs in 118 candidate genes selected from the literature (e.g., dopamine, serotonin, glutamate, and GABA pathways) and composite genotypes for 10 drug-metabolizing enzymes. No single marker or haplotype association reached statistical significance after adjustment for multiple comparisons. Thus, we found no support for either novel or prior associations from the literature. PMID- 19475586 TI - 2,7-Di-tert-butylnaphtho[1,8-cd][1,2]dithiole 1,2-dioxides: thermally stable, photochemically active vic-disulfoxides. AB - Bulking up: The thermal barrier to rearrangement of a vic-disulfoxide is significantly increased through steric buttressing about the (O)S--S(O) bond. Whereas the title compounds represent the most thermally stable vic-disulfoxides known to date, they also undergo a novel photomediated epimerization at room temperature (see scheme). PMID- 19475588 TI - Click chemistry beyond metal-catalyzed cycloaddition. AB - The overwhelming success of click chemistry encouraged researchers to develop alternative "spring-loaded" chemical reactions for use in different fields of chemistry. Initially, the copper(I)-catalyzed azide-alkyne cycloaddition was the only click reaction. In recent years, metal-free [3+2] cycloaddition reactions, Diels-Alder reactions, and thiol-alkene radical addition reactions have come to the fore as click reactions because of their simple synthetic procedures and high yields. Furthermore, these metal-free reactions have wide applicability and are physiologically compatible. These and other alternative click reactions expand the opportunities for synthesizing small organic compounds as well as tailor-made macromolecules and bioconjugates. This Minireview discusses the success and applicability of new, in particular metal-free, click reactions. PMID- 19475590 TI - Time-resolved in situ synchrotron X-ray study and large-scale production of magnetite nanoparticles in supercritical water. AB - A general solution: In situ synchrotron X-ray scattering in a high-pressure pulsed injection reactor (see picture) shows that magnetite nucleation and growth are temporally separated. Gram-scale crystalline, pure phase, superparamagnetic magnetite nanoparticles were synthesized without surfactants in supercritical water in less than one hour using a laboratory-scale continuous-flow reactor. PMID- 19475591 TI - Holographic fabrication of microstructures with internal nanopatterns using microprism arrays. PMID- 19475592 TI - Combined NMR and UV/vis spectroscopy in the solution state: study of the geometries of strong OHO hydrogen bonds of phenols with carboxylic acids. PMID- 19475593 TI - Synthesis and pp60c-Src tyrosine kinase inhibitory activities of novel indole-3 imine and amine derivatives substituted at N1 and C5. AB - A series of novel 1,3,5-trisubstituted indole derivatives, namely, N-benzyl 5 phenyl indole-3-imine, N-benzyl-5-(p-fluorophenyl)indole-3-imine and their corresponding amine congeners, were designed and synthesized as pp60(c-Src) tyrosine kinase inhibitors, and their inhibitory activities toward pp60(c-Src) tyrosine kinase were evaluated by in-vitro kinase assay. Pre-screening at two doses of compounds against kinase target revealed that, except for the N-benzyl-5 phenyl indole imine derivatives 7a-7d, all indole derivatives show the target inhibition at varying levels. Consequently, the compounds, 8c, 8f, 8g, and 8h, were selected for prescreening tests. The dose-response curves for up to six concentrations (250 to 7.8 muM) of the active compounds were obtained by tyrosine kinase assay and the four-parameter logistic analysis of these data resulted in the IC(50)s of 4.69, 74.79, 75.06, and 84.23 muM for compounds 8c, 8f, 8g, and 8h, respectively. Therefore, compound 8c, 1-(1-benzyl-5-phenyl-1H-indole-3-yl)-N (4-fluorobenzyl)methanamine.HCl, was the promising inhibitor for pp60(c-Src), followed by compounds 8g and 8h. Under the same conditions, compound 8f did not provide any reasonable inhibition pattern to be considered as active compound. Therefore, among all four active compounds, compound 8f was not found suitable for further analysis. PMID- 19475594 TI - Dietary phenolics, absorption, mammalian and microbial metabolism and colonic health. PMID- 19475595 TI - Synthesis and antibacterial activity of a new series of 3-[3-(substituted phenyl) 1-isonicotinoyl-1H-pyrazol-5-yl]-2H-chromen-2-one derivatives. AB - A novel series of 3-[3-(substituted phenyl)-1-isonicotinoyl-1H-pyrazol-5-yl]-2H chromen-2-one derivatives 4a-k have been synthesized by the reaction of 3-[2,3 dibromo-3-(substituted phenyl) propanoyl]-2H-chromen-2-one 3a-k and isonicotinic acid hydrazide in the presence of triethylamine in absolute ethanol, characterized by spectral data and screened for their in-vitro antibacterial activity against Gram-positive and Gram-negative bacteria. Among the series, compounds 4e, 4i, and 4k displayed an encouraging antibacterial activity profile as compared to the reference drug ampicillin against tested bacterial strains. PMID- 19475596 TI - Generation and evaluation of a homology model of PfGSK-3. AB - Plasmodial GSK-3 is a potential new target for malaria therapy. For a structure based design project, the three-dimensional information of the designated target is needed. Unfortunately, experimental structure data for plasmodial GSK-3 is not yet available. Homology building can be used to generate such three-dimensional structure data using structure information of a homologous protein. GSK-3 possesses a very flexible ATP-binding site, a fact reflected in the variety of X ray structures of the human GSK-3beta which are deposited in the protein data base and are crystallized with different ligands. We used ten different HsGSK 3beta templates for the model building of plasmodial GSK-3 and generated 200 models for each template with different modeling protocols. The quality of the models was evaluated with different tools. The results of these evaluations were used to calculate a rank-by-rank consensus score. The top models of this were used to compile an ensemble of PfGSK-3 models that reflect the flexibility of the ATP-binding site and that will be used for the structure-based design of potential ATP-binding site inhibitors of PfGSK-3. PMID- 19475597 TI - Structural link between giant molybdenum oxide based ions and derived Keggin structure: modular assemblies based on the [BW11O39]9- ion and pentagonal {M'M5} units (M' = W; M = Mo,W). AB - Linked to the Pentagon: The addition of molybdate to [HBW(11)O(39)](8-) ions leads to the formation of mixed pentagonal units {W(Mo(5))} and {W(WMo(4))} trapped as linkers in the resulting modular assemblies, thus establishing the first link between the conventional Keggin ion derivatives and the giant molybdenum oxide and keplerate ions. PMID- 19475599 TI - Titanium binolate catalyzed aminolysis of meso aziridines: a highly enantioselective and direct access to 1,2-diamines. AB - It's as simple as that: An in situ prepared chiral catalyst from the commercially available compounds Ti(OiPr)(4) and (R)-binol catalyzes the highly enantioselective ring-opening of meso-aziridines 1 with anilines 2 and furnishes valuable chiral 1,2-diamines 3 in high yields and up to 99 % ee.(R)-binol=(R) 2,2'-dihydroxy-1,1'-binaphthyl. PMID- 19475598 TI - Symmetry-guided design and fluorous synthesis of a stable and rapidly excreted imaging tracer for (19)F MRI. AB - Getting FIT: A bispherical (19)F imaging tracer, (19)FIT, was designed and synthesized. (19)FIT is advantageous over perfluorocarbon-based (19)F imaging agents, as it is not retained in the organs and does not require complex formulation procedures. Imaging agents such as (19)FIT can lead to (19)F magnetic resonance imaging (MRI) playing an important role in drug therapy, analogous to the role played by (1)H MRI in disease diagnosis. PMID- 19475600 TI - A graphene platform for sensing biomolecules. AB - Sensitive platform: The use of graphene oxide (GO) as a platform for the sensitive and selective detection of DNA and proteins is presented. The interaction of GO and dye-labeled single-stranded DNA leads to quenching of the dye fluorescence. Conversely, the presence of a target DNA or protein leads to the binding of the dye-labeled DNA and target, releasing the DNA from GO, thereby restoring the dye fluorescence (see picture). PMID- 19475601 TI - Novel extreme homozygote haplotypes at the human caveolin 1 gene upstream purine complex in sporadic Alzheimer's disease. AB - Aberrant expression of the caveolin-1 (CAV1) gene is associated with Alzheimer's disease (AD) brain. We have recently reported a polymorphic purine stretch located at between 1.8 and 1.5 kb flanking the CAV1 gene, whose alleles and genotypes are associated with late-onset AD. Extra-short homozygote haplotypes were observed that were present only in the AD cases. Following an independent case/control study, we report alleles at the other extreme of the allele range, haplotypes of which were observed to be homozygous across the region in the AD cases. We propose that there is a window for the length of motifs and haplotypes in the controls. Homozygosity for shorter and longer motifs and haplotypes was linked with AD in our study. Our findings elucidate novel predisposing haplotypes at the CAV1 gene purine complex, and confirm the role of this region in the etiopathophysiology of late-onset AD. PMID- 19475602 TI - No evidence of an association between two genes, EDN1 and ACE, and childhood onset mood disorders. AB - Recent evidence supports a pathological link between heart disease and depressive symptoms, suggesting that depression is both etiologic and prognostic to heart disease. Thus, biological molecules which are at the interface between heart and mind are plausible candidate genes for depressive disorders. To investigate this line of enquiry we have investigated two genes, Endothelin 1 (EDN1) and Angiotensin-converting enzyme (ACE) in a family-based sample with childhood-onset mood disorders (COMDs). EDN1 is highly expressed in endothelium where it acts as a potent vasoconstrictor, and is also expressed in the brain where it exhibits neurotransmitter characteristics. ACE acts as a potent vasopressor, and interacts with the hypothalamic-pituitary-adrenocortical (HPA) system, which is often dysregulated in mood disorders. Furthermore, ACE has recently been found to be associated with major depression. Polymorphisms were selected to best capture the genetic variation at the two loci, and to replicate previous associations. The markers were genotyped across EDN1 and ACE in a sample comprised of 382 Hungarian nuclear families ascertained through affected probands diagnosed with a mood disorders before the age of 15. We found no evidence of association between either of these genes and COMD. Consequently, we were unable to support our hypothesis that these two genes, which are involved in both vascular and brain functions are contributing to the susceptibility to mood disorders of children/adolescents. PMID- 19475603 TI - Hepatitis C virus infection in the family setting of patients with occult hepatitis C. AB - Family members of patients with chronic hepatitis C virus (HCV) infection are at increased risk of HCV infection but the prevalence of HCV among family members of patients with occult HCV infection is not known. Anti-HCV, serum HCV RNA and levels of liver enzymes were determined in 102 family members of 50 index patients with occult HCV infection and in 118 family members of 59 chronic hepatitis C index patients. HCV RNA and/or anti-HCV were detected in 10/102 (9.8%) relatives of patients with occult HCV infection and in 4/118 (3.4%) of patients with chronic hepatitis C. Fourteen additional family members (seven were relatives of index patients with occult HCV infection) had abnormal values of liver enzymes without serological markers of HCV infection. Two of these patients (who were relatives of two index patients with occult HCV infection) underwent a liver biopsy and were diagnosed with an occult HCV infection because HCV RNA was detected in the liver cells in the absence of serological HCV markers. In conclusion, the prevalence of HCV infection among family members of patients with occult HCV infection was similar to that found among family members of patients with chronic hepatitis C. This stresses the need to adopt strategies to prevent the transmission of HCV in the family setting of patients with occult HCV infection. PMID- 19475604 TI - Hepatitis C virus screening and clinical monitoring of biomarkers in patients undergoing hemodialysis. AB - In this study, 395 volunteers were enrolled to investigate the seroprevalence of hepatitis C virus, the immunological and the alanine aminotransferase (ALT) biomarkers amongst hemodialysis patients, living in Manaus, Brazil. An overall seroprevalence of 13.9% was found in the hemodialysis patients. Analysis of seroconversion patterns demonstrated that most patients with HCV seroconverted up to 10 years following the first hemodialysis session. Anti-NS5 antibody was detectable in 60.4% of patients with HCV. A lower percentage of circulating CD3(+) and CD4(+) T-cells was found in patients seronegative for HCV, whereas a higher frequency of CD8(+) T-cells was the hallmark of patients with HCV. An overall low activation state of monocytes and eosinophils were observed in hemodialysis patients. In contrast, a higher frequency of activated neutrophils was observed in patients with HCV, selectively in the NS5+ subgroup. All hemodialysis patients had a higher percentage of activated lymphocytes, with the higher activation state in patients with NS5- reactivity. Higher ALT levels were observed in patients with HCV, especially in the NS5+ subgroup. Interestingly, the ALT levels were correlated negatively with the lymphocyte activation state, selectively in the NS5- subgroup, suggesting a protective role of these activated lymphocytes in patients with HCV. These findings reinforce the importance of the transmission of HCV among hemodialysis patients, suggesting that apart from the HCV screening, the serological and ALT biomarkers may represent important predictors of morbidity and/or mortality among patients undergoing hemodialysis. PMID- 19475606 TI - Evidence that methylation of hepatitis B virus covalently closed circular DNA in liver tissues of patients with chronic hepatitis B modulates HBV replication. AB - Epigenetic factors may modulate chronic Hepatitis B viral infection by affecting virion gene transcription. The aim of this study was to compare the methylation status of the intrahepatic covalently closed circular DNA (cccDNA) CpG island 2 and HBV replication capability. HBV cccDNA was extracted from liver biopsies of 55 HBsAg-positive patients with chronic hepatitis B (32 HBeAg-positive and 23 HBeAg-negative), and was analyzed for methylation status and quantity. The two Hpa II recognition sequences CCpGG in the CpG island 2 were methylated in infected liver tissues from 24 (43.6%) of 55 patients. Positive ratios of cccDNA methylation were significantly higher in HBeAg-negative patients (15/23, 65.2%) than HBeAg-positive patients (9/32, 28.1%) (P < 0.05). The percentage of methylated-cccDNA/total-cccDNA of HBeAg-negative samples (a median of 48%, ranging from 5% to 83%) was significantly higher (P < 0.001) than HBeAg-positive samples (a median of 14%, ranging from 0.26% to 35%). Ratios of relaxed circular DNA (rcDNA) to cccDNA molecules revealed that cccDNA methylation correlated with impaired virion productivity in HBeAg-positive individuals (P < 0.05). The bisulfite DNA sequencing showed that methylation density was significantly higher in HBeAg-negative than in HBeAg-positive patients (P < 0.05). The methylation level of the CpG island 2 of the cccDNA in HBeAg-negative patients was higher than that in HBeAg-positive patients, suggesting that HBV cccDNA methylation may be relevant to replication capability of HBV. PMID- 19475605 TI - Clinical evaluation of highly pathogenic tick-borne flavivirus infection in the mouse model. AB - The objective of this study was to evaluate the feasibility of using clinical parameters to demonstrate disease progression and differentiate between Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) infection in the mouse model. Adult C57BL/6 and balb/c mice were infected with either OHFV or RSSEV by footpad inoculation and their temperature, body weight, clinical signs complete blood count, and blood chemistries were evaluated for up to 15 days post-infection (dpi). Clinical evaluation showed that OHFV infection seriously affects balb/c mice, which had shorter average survival times (ASTs) than other groups. On the contrary, RSSEV infection of C57BL/6 mice was more severe than in balb/c mice. During these studies, the development of fever was not observed and the body weight of OHFV infected balb/c and C57BL/6 mice began to decline sharply starting from day 7 and 8, respectively, which correlated with disease onset. Peak increase of globulin and neutrophils was demonstrated after 9 dpi in OHFV infected mice; however, the lymphocyte number was not affected. Viremia was undetectable in these animals with either virus infection, but virus was found in most organs tested. These results indicate marked differences in the clinical signs, pathology, and immune response of mice infected with either OHFV or RSSEV and further validate the use of this mouse model system to evaluate human disease. PMID- 19475607 TI - Population-based study on the seroprevalence of parvovirus B19 in Amsterdam. AB - A study was undertaken to estimate the seroprevalence of parvovirus B19 infection in the general adult population of Amsterdam, The Netherlands. To our knowledge this is the first study testing parvovirus B19 in a random sample of the Dutch adult population. The study was a cross-sectional survey, and the study sample was stratified by age and ethnicity, with deliberate oversampling of minority ethnic groups. Serum samples obtained from 1,323 residents in 2004 were tested for antibodies to parvovirus B19. Basic demographic data (gender, age, country of birth, and number of children) were also available. Sixty-two percent of the participants were seropositive; corrected for the oversampling the estimated prevalence in the Amsterdam adult population was 61%. No specific predictors or risk groups for seropositivity were identified. In our urban adult study population no positive correlation with increasing neither age, nor significant differences between age groups were found. These results imply that almost 40% of the adult Amsterdam population is susceptible to infection. J. Med. Virol. 81:1305-1309, 2009. (c) 2009 Wiley-Liss, Inc. PMID- 19475608 TI - Characterization of cytotoxic T-lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD-integrin-binding motif. AB - Integrins are critical for initiating T-cell activation events. The integrin binding motif Arg-Gly-Asp (RGD) was incorporated into the pcDNA 3.1 mammalian expression vector expressing the codon-optimized extracellular domain of SARS coronavirus (SARS-CoV) spike protein, and tested by immunizing C57BL/6 mice. Significant cell-mediated immune responses were characterized by cytotoxic T lymphocyte (51)Cr release assay and interferon-gamma secretion ELISPOT assay against RMA-S target cells presenting predicted MHC class I H2-Kb epitopes, including those spanning residues 884-891 and 1116-1123 within the S2 subunit of SARS-CoV spike protein. DNA vaccines incorporating the Spike-RGD/His motif or the Spike-His construct generated robust cell-mediated immune responses. Moreover, the Spike-His DNA vaccine construct generated a significant antibody response. Immunization with these DNA vaccine constructs elicited significant cellular and humoral immune responses. Additional T-cell epitopes within the SARS-CoV spike protein that may contribute to cell-mediated immunity in vivo were also identified. PMID- 19475610 TI - Sequence and structural analysis of the 5' noncoding region of hepatitis C virus in patients with chronic infection. AB - Hepatitis C virus (HCV), exhibits considerable genetic diversity, but presents a relatively well conserved 5' noncoding region (5' NCR) among all genotypes. In this study, the structural features and translational efficiency of the HCV 5' NCR sequences were analyzed using the programs RNAfold, RNAshapes and RNApdist and with a bicistronic dual luciferase expression system, respectively. RNA structure prediction software indicated that base substitutions will alter potentially the 5' NCR structure. The heterogeneous sequence observed on 5' NCR led to important changes in their translation efficiency in different cell culture lines. Interactions of the viral RNA with cellular transacting factors may vary according to the cell type and viral genome polymorphisms that may result in the translational efficiency observed. PMID- 19475611 TI - A neuropsychological study comparing patients infected with HCV and HBV without psychiatric comorbidities. AB - Hepatitis C is one of the most common chronic infectious diseases worldwide, with well-documented extra-hepatic manifestations, such as a broad number of cognitive deficits. These impairments may be explained by psychiatric comorbidities, which have not been investigated properly in the literature. In order to elucidate a specific hepatitis C virus (HCV) induced cognitive impairment not related to mental disorders, neuropsychological performance of patients infected with HCV was compared with that of patients infected with hepatitis B virus cognitive impairment, especially psychiatric comorbidities. A total of 33 patients infected with HCV and 22 patients infected with HBV were included in the study. There were no significant differences between the two groups with regard to age or years of education. The group of patients infected with HCV performed significantly worse on visuo-spatial memory tasks after adjusting for years of education and age. There were no significant differences between patients infected with HCV and patients infected with HBV with regards to other neuropsychological functions. The data indicate that patients infected with HCV patients have poorer visuo spatial memory performance than patients infected with HBV, suggesting that the cognitive deficit may be specific to HCV infection and not to secondary comorbid psychiatric disorders. PMID- 19475612 TI - HPV genotype prevalence in women with abnormal pap smears in Melbourne, Australia. AB - Carcinoma of the cervix and its precursor, high-grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent oncogenic Human papillomavirus (HPV) infection, particularly HPV 16 and 18. HPV genotype distribution varies with severity of cervical disease, patient demographics such as age, as well as geographical location. In this study, HPV genotype prevalence was determined, using the Roche Linear Array genotyping test, among a cohort of 1,676 women being managed with ablative or excisional treatment following colposcopically directed biopsies, who were referred initially due to cytological abnormalities. HPV genotype prevalence, including presence of single and multiple infections was assessed against both histological diagnosis and age. Overall, 83.9% of women were identified as HPV positive, comprising of 32.2% single and 51.7% multiple HPV infections. Of those with an available histological diagnosis at time-of treatment (n = 899), HPV positivity increased significantly with disease severity: 62.4% (normal), 77.6% (CIN1), 92.6% (CIN2), and 97.9% (> or =CIN3) (P < 0.006). Similarly, a significant increase in high-risk (HR) HPV detection was observed with severity of disease (P < 0.005). The five most prevalent genotypes were HPV 16 (35.1%), 31 (12.6%), 51 (11.1%), 52 (9.9%), and 18 (8.5%). HPV 16 was the only genotype to demonstrate a significant increase in prevalence with increasing severity of histological or cytological disease (P < 0.0001). Multiple HPV infections, including multiple HR-HPV infections, declined significantly with age (P < 0.02). These findings provide the largest dataset of HPV genotype prevalence rates within Australian women, though are not representative of the general population. PMID- 19475609 TI - A real-time PCR assay to identify and discriminate among wild-type and vaccine strains of varicella-zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. AB - A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human beta-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results. PMID- 19475614 TI - Tracking the transmission routes of genogroup II noroviruses in suspected food borne or environmental outbreaks of gastroenteritis through sequence analysis of the P2 domain. AB - The aim of this study was to apply sequence analysis of a hyper variable region of the norovirus (NoV) genome in order to identify point source outbreaks associated with suspect food or water. The hyper-variable region of the gene encoding the P2 domain was chosen as small differences in sequence are likely to indicate virus from different sources whereas identical sequence may reveal transmission routes and the source of contamination. Strains with 100% similarity were considered as originating from a common source, whereas, strains with one or more mutations in the hyper variable region sequenced were regarded as representing unrelated transmission events. This study was able to identify a point source outbreak of a dominant strain, GII-4, on a cruise ship but also of a less common strain, GII-2, between two schools. Also identical GII-3 strains were demonstrated in food handlers amongst the same outbreak; however epidemiologically related outbreaks showed different GII-3 strains indicating multiple sources of contamination. PMID- 19475615 TI - A peptide derived from hepatitis C virus (HCV) core protein inducing cellular responses in patients with HCV with various HLA class IA alleles. AB - C35-44 peptide is a well known HLA-A2-restricted CTL epitope originating from hepatitis C virus (HCV) core protein. It was reported that the majority of HCV positive patients had significant levels of serum IgG specific to this peptide. This study addressed whether C35-44 peptide could induce CTL activity restricted to various HLA class IA alleles or could not. This peptide demonstrated binding activity to HLA-A*2402, -A*2601, -A*3101, and -A*3303 molecules, but not to HLA A*1101 by means of stabilization assay. This peptide also induced CTL activity restricted to each of them, except HLA-A11(+) peripheral blood mononuclear cells from HCV 1b(+) patients by means of (51)Cr-release assay. With regard to HLA-A2 subtypes, this peptide demonstrated binding activity to HLA-A*0201 and -A*0206, but not to -A*0207 molecules. Furthermore, this peptide induced CTL activity from both the patients and healthy donors with all the HLA class IA molecules mentioned above by means of interferon-gamma production assay. These results may provide new insights for the development of a novel peptide vaccine against HCV compatible with various HLA class IA types. PMID- 19475613 TI - Tracking the entry routes of hepatitis C virus as a surrogate of HIV in an HIV low prevalence country, the Philippines. AB - From 2002 to 2007, 1,590 individuals were enrolled in an active surveillance program conducted in Metro Cebu, Philippines, where the anti-HCV-positive rate was significantly and constantly high among injecting drug users (83%, 793/960; 71-88%), especially among those living in downtown (89%, 683/770; 87-100%), despite the extremely low percentage of anti-HIV-positives (0.34%, 3/874). Sampling areas were then enlarged nationwide and the number of samples increased to 2,645 at the end of 2007. A total of 444 samples were positive for HCV RNA. Phylogenetic analysis based on NS5B and E1-E2 regions revealed that the most dominant HCV subtype was 1a, and followed by 2b, 2a, and 1b, and that the HCV strains had the largest variety in Metro Manila and its vicinity (P < 0.01). Interestingly, subtype 1b was detected solely in Metro Manila, and four HCV strains collected in this area showed higher homology to specific foreign strains retrieved from the Genbank/EMBL/DDBJ database with bootstrap values of 68-95% comparing with other strains analyzed in this nationwide study. These data suggest that HCV strains may be introduced occasionally into the Philippines possibly through Metro Manila as a main entry point. Considering the fact that an HIV epidemic started primarily via contaminated needle sharing in Asia, the constantly high rate of HCV infections and the newly introduced foreign HCV strains in the absence of HIV epidemic warrant further investigation on HCV entry and spread for early detection of an HIV epidemic in the Philippines. PMID- 19475616 TI - High prevalence of human papillomavirus type 58 in patients with cervical pre malignant lesions in southern Brazil. AB - Cervical cancer is the second most common type of cancer in women worldwide. Several human papillomavirus (HPV) genotypes, sexual behavior, and socioeconomic profile represent major risk factors for the development of this carcinoma. Cervical invasive cancer is preceded by cellular abnormalities that can be identified by cytological or histological exams. In order to determine the prevalence and genotypes of HPV in women with abnormal cytology or histopathology, cervical cell samples from 256 patients were evaluated for the presence of HPV/DNA by polymerase chain reaction (PCR), followed by virus genotyping by restriction fragment length polymorphism (RFLP). A total of 113 samples (51.2%) were HPV/DNA positive. Viral genotyping showed that the most prevalent genotypes were HPV 16 (34.7%) and 58 (13.8%), followed by HPV 33 (9.72%), 11 (8.33%), 18 (5.55%), 53 (5.55%), and 6 (4.2%). Four samples (5.55%) exhibited multiple infections due to the great similarity of socioeconomic characteristics and sexual behavior of HPV positive women, it was not possible to establish a risk profile for female HPV infection. PMID- 19475617 TI - Epidemic spread of hepatitis C virus genotype 3a and relation to high incidence of hepatocellular carcinoma in Pakistan. AB - Studies conducted in different populations worldwide revealed an association between HCV genotype 1 and the development of hepatocellular carcinoma (HCC) than in infection with other HCV genotypes. There are reports which reveal the association of HCV genotype 3a (HCV-3a) with hepatic steatosis and fibrosis but its relation with the development of HCC has not been investigated. In Pakistan, where the incidence of HCC is increasing, 189 patients with chronic liver disease including 82 with HCC were enrolled. HCV genotypes were determined by phylogeny in the NS5B region and the epidemic history of HCV-3a was examined using coalescent theory based methods. HCV-3a was the predominant genotype (81.4%) in the cohort studied, followed by 3b (9.3%), 3k (2.3%), 1a (1.5%), 1c (1.5%), 1b (0.8%), and 2a (0.8%) where 76% of HCC and 86% of non-HCC were infected with HCV 3a. The significant factors associated with HCC were older age (mean +/- SD) 55.8 (+/-9.9) (P < 0.0001), and male gender (P < 0.001). HCV RNA was significantly higher in patients with HCC and chronic hepatitis than in liver cirrhosis (P < 0.0001). Molecular evolutionary analysis revealed a distinct phylogenetic cluster of HCV-3a in Pakistan and an estimation of the effective number of HCV infections indicated the appearance of HCV-3a in this region around 1920s and a rapid exponential growth in the 1950s. This indicates that the epidemic spread of HCV 3a occurred earlier in Pakistan than in other countries in which this genotype has been reported. HCV-3a which spread earlier in Pakistan may be associated with an increasing incidence of HCC. PMID- 19475618 TI - TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C. AB - Phenotypes of liver disease due to chronic hepatitis C virus (HCV) infection show a wide range of variations in terms of histological manifestations and the clinical outcome. Sensing of viral double-stranded RNA (dsRNA) by Toll-like receptor 3 (TLR3) is likely involved in early pathogen detection and the host response to viral infection. This study analyzed epidemiological and clinical data from a total of 137 patients with chronic HCV infection with regard to two polymorphic positions within the TLR3 gene: rs5743305 (T/A) is located within the promoter region and might affect transcriptional activity, rs3775291 (C/T) is a non-synonymous single nucleotide polymorphism (SNP) located within exon 4 and the variant receptor has been shown to be functionally impaired. TLR3 promoter and the exon 4 variations were not found to be associated with TLR3 gene expression in peripheral blood mononuclear cells (PBMCs). In the liver, however, a tendency of higher TLR3 gene expression was found for exon 4 TT genotypes. Both variations were not found to be associated with clinical parameters of chronic disease. On the other hand, an analysis of the TLR3 exon 4 genotype distribution with respect to HCV subtype revealed an absence of TT genotype among HCV subtype 1a infected individuals. This study thus failed to reveal any association of the two SNPs under investigation with clinical parameters of chronic hepatitis C. However, data argue for a functional relevance of the exon 4 SNP in terms of conferring a different susceptibility towards HCV subtype infection. PMID- 19475620 TI - Molecular analysis of HPV 16 E6I/E6II spliced mRNAs and correlation with the viral physical state and the grade of the cervical lesion. AB - The presence of HPV 16 E6*I/E6*II spliced transcripts, in cervical lesions of different grade, was analyzed to characterize the transcription pattern. The presence and amount of spliced transcripts were correlated with DNA viral markers such as E2/E6 ratio and physical state. The detection of HPV 16 E6*I/E6*II mRNAs was set up by an SYBR Green real-time reverse transcriptase PCR assay with an optimal dynamic range and sensitivity. The assay was applied to the analysis of 71 specimens, positive to HPV 16 as a sole infection, from women with abnormal cervical smears, precisely 31 low-grade squamous intraepithelial lesions and 40 high-grade lesions. Samples negative to both transcripts were found only in low grade cervical lesions. Three different transcription profiles were found in the low- and high-grade lesions analyzed: in low-grade lesions samples positive only to E6*II and in high-grade lesions samples positive only to E6*I were detected. In low- and high-grade lesions, samples positive to both E6*I and E6*II were found. In the samples positive for both transcripts, the E6*I/E6*II ratio was higher than that in the majority of high-grade lesions and lower than that in all the low-grade lesions. Analyzing the transcription pattern in relation to E2/E6 ratio and to the DNA physical state, the presence of high values of E6*I was associated mainly with low values of E2/E6 ratio and of mixed DNA forms. The detection of HPV 16 E6*I/E6*II mRNAs may serve to identify transcription patterns indicative of cervical disease progression and help physicians to decide clinical management. PMID- 19475619 TI - Investigation of pre-diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus-infected patients. AB - Progressive multifocal leukoencephalopathy (PML) is a severe neurological disorder due to JC virus (JCV) infection. Pre-diagnostic biological markers and risk factors for PML are not well understood. We conducted a case-control study nested within the Multicenter AIDS Cohort Study to examine the association between JCV viruria and viremia and serum antibody to JCV capsids, in relation to subsequent PML diagnoses, 5 months to 12 years later. Other demographic and immunologic factors were also examined. The study population included 28 incident cases of PML, 26 matched HIV-positive controls, and 50 HIV-negative controls. Prevalence of JCV viruria was 37% in cases, 42% in HIV-positive controls, and 28% in HIV-negative controls (P = 0.43). Among persons with JCV viruria, persistent viruria was more common in cases (89%) than in HIV-positive controls (33%) (P = 0.02). Presence of JCV viruria was not related to the time to PML diagnosis (OR: 1.03, 95% CI: 0.8-1.4); however, the urinary concentration of JCV DNA increased with proximity to the date of PML diagnosis in cases. JCV seropositivity did not differ between cases or controls (P = 0.42). Four cases tested JCV seronegative, including one case only 5 months prior to diagnosis with PML. JCV DNA was detected in the serum of one HIV-positive control. Smoking was the only demographic variable analyzed associated with an increased risk for PML (MOR: 9.0, 95% CI: 1.2-394.5). The results suggest that persistent JCV viruria and increasing urinary concentration of JCV DNA may be predictive of PML for some patients. PMID- 19475621 TI - Enterovirus 71-induced autophagy detected in vitro and in vivo promotes viral replication. AB - Enterovirus 71 (EV71) is an important pathogen causing death in children under 5 years old worldwide. However, the underlying pathogenesis remains unclear. This study reveals that EV71 infection in rhabdomyosarcoma (RD) and neuroblastoma (SK N-SH) cells stimulated the autophagic process, which was demonstrated by an increase of punctate GFP-microtubule-associated protein 1 light chain 3 (GFP LC3), the level of autophagosome-bound LC3-II protein and double-membrane autophagosome formation. EV71-induced autophagy benefited EV71 replication, which was confirmed by the autophagic inducer rapamycin and the inhibitor 3 methyladenine. Signaling pathway investigation revealed that the decreased expression of phosphorylated mTOR and phosphorylated p70S6K is involved in EV71 induced autophagy in a cell-specific manner. The expression of phosphorylated extracellular signal-regulated kinase (Erk) was suppressed consistently in EV71 infected cells. However it did not participate in the autophagic response of the cell. Other signaling pathway molecules, such as Erk, PI3K/Akt, Bcl-2, BNIP3, and Beclin-1 were not affected by infection with EV71. Electron microscopy showed co localization of autophagosome-like vesicles with either EV71-VP1 or LC3 protein in neurons of the cervical spinal cord in ICR mice infected with EV71. In conclusion, EV71 infection triggered autophagic flux and induced autophagosome formation both in vitro and in vivo. Autophagy induced by EV71 is beneficial for viral replication. Understanding the role of autophagy induced by EV71 in vitro and the formation of autophagosome-like vesicle in vivo provide new insights into the pathogenesis of EV71 infection. PMID- 19475622 TI - The dominance of China 1 in the spectrum of Epstein-Barr virus strains from Cantonese patients with nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma is a disease with a remarkable geographic and ethnic distribution, and has a high incidence in southern China. Infection with Epstein Barr virus (EBV) is an important contributing factor. The profile of EBV strains in Cantonese patients from Guangdong, the nasopharyngeal carcinoma endemic region in southern China, is described on the sequence variations in latent membrane protein 1 carboxyl-terminus. The results show that China 1 was the dominant EBV strain detected in both the tumor biopsies and samples of throat washings, whereas multiple strains, including China 1, China 2, B95-8, and Med, were detected in blood samples. In addition, a new strain named China 4 was found in blood samples. These findings suggest that the host population is susceptible to the predominant China 1 strain in the nasopharyngeal carcinoma endemic region of China, but its relationship with the host remains to be characterized further. PMID- 19475624 TI - Effect of HIV co-infection on mutation patterns of HBV in patients with lamivudine-resistant chronic hepatitis B. AB - A retrospective review was performed comparing lamivudine-resistance mutation patterns between patients infected with hepatitis B virus (HBV) with or without human immunodeficiency virus (HIV) co-infection. Medical records that included a genotypic test of patients infected with HBV and treated with lamivudine as the only anti-HBV drug were reviewed. Pol gene mutations were assessed by direct sequencing of the reverse transcriptase fragment 125-213 aa. Eighty-nine patients infected with HBV (29 co-infected with HIV) with rtM204V or rtM204I mutations were included. Multiple mutations associated with the YMDD motif were observed in 33 (55%) of 60 patients infected with HBV only and in 28 (96.6%) of patients co infected with HIV/HBV. In this latter group, the prevalence of the rtV173L + rtL180M + rtM204V triple mutation was 31% versus a prevalence of 3.4% observed among patients infected with HBV only. All patients with the triple mutational pattern showed sE164D + sI195M changes in the envelope gene. Multivariate analysis demonstrated that HIV co-infection (adjusted OR 11.2, 95% CI 2.0-61.0) and HBV genotype A (adjusted OR 7.2, 95% CI 1.5-34.8) were the only independent variables associated with the chance of harboring rtM204V. Patients with HBV genotype A or HIV co-infection were more likely to harbor the rtM204V mutation. Patients co-infected with HIV showed multiple mutations more frequently, including the triple mutation that may elicit a vaccine escape phenotype. Among patients co-infected with HIV/HBV, strict HBV DNA monitoring is essential to detect treatment failure and adapt therapy to avoid limitations of future therapeutic options or the emergence of a public health threat. PMID- 19475623 TI - Two decades of hepatitis B infections among drug users in Amsterdam: are they still a high-risk group? AB - In general, little is known about the incidence of hepatitis B virus (HBV) among drug users, especially among non-injecting drug users. Therefore, changes in incidence, risk factors, and circulating genotypes over time were determined among drug users in Amsterdam over an 18-year period (1985-2002). Sera of 1,268 drug users, both injecting and non-injecting, were screened for anti-HBc. HBV genotypes of the anti-HBc seroconverters were determined. Poisson regression was used to test for temporal trends in incidence and to identify risk factors for seroconversion. Of the 598 participants who were anti-HBc negative at entry, 83 seroconverted for anti-HBc. The incidence of HBV declined from 5.9/100 Person Years up to 1993 to 0/100 Person Years in 2002. Of the drug users infected acutely, both injecting and non-injecting, 88% were infected with the same genotype D, serotype ayw3 strain. Multivariate analyses revealed current injecting, age, and calendar year of visit as independent risk factors. The decline in the incidence of HBV among drug users in Amsterdam is probably caused by a decline in injecting behavior. Injecting and non-injecting drug users were infected with the same strain, indicating that drug users infect one another, regardless of their risk behavior. After 2000, no injecting drug users with an acute HBV infection were reported to the Public Health Service Amsterdam and the specific genotype D strain had disappeared. These findings suggest that drug users may no longer be a high-risk group for HBV infection in Amsterdam. However, trends in drug use need to be monitored. PMID- 19475625 TI - Antioxidant enzymes and melatonin levels in patients with bronchial asthma and chronic obstructive pulmonary disease during stable and exacerbation periods. AB - An imbalance between oxidative stress and antioxidative capacity may play an important role in the development and progression of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). We carried out a study to assess the systemic oxidant-antioxidant status during the exacerbation and the stable period in patients with BA and COPD. A total of 33 patients, 16 with BA and 17 with COPD were included in the study. During the exacerbation and the stable periods, levels of malondialdehyde (MDA), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GRd), and catalase (CAT) in erythrocytes and serum melatonin concentrations were investigated. Blood counts, respiratory functions, and blood gases of the patients were also performed. During an exacerbation period of BA, despite the decreases in GSH-Px, GRd and melatonin levels, MDA and CAT levels, and the white blood cell count, the percentage of eosinophils were significantly higher than in the stable period. Also, it was found that FEV(1)/L (where FEV(1) is the forced expiratory volume in 1 s), FVC/L (where FVC is forced vital capacity), PEF/L/s (where PEF is peak expiratory flow), pO(2) (where pO(2) is oxygen pressure) levels increased during the stable period in patients with BA. MDA and SOD values were higher in the exacerbation period than in the stable period although GSH-Px, GRd, melatonin, pH, and pO(2) values were lower in the exacerbation period than in the stable period. The blood counts and the respiratory function tests did not change between the exacerbation and the stable period of patients with COPD significantly. In conclusion, we observed that oxidative stress in the exacerbation period of patients with BA and COPD increased whereas the antioxidant enzymes and melatonin values reduced. The episodes of BA or COPD might be associated with elevated levels of oxidative stress. PMID- 19475626 TI - Premarital screening for thalassemia in mainland China. PMID- 19475627 TI - Three- and four-dimensional visualization of cell migration using optical coherence tomography. AB - Conventionally, cell chemotaxis is studied on two-dimensional (2D) transparent surfaces, due to limitations in optical and image data-collection techniques. However, surfaces that more closely mimic the natural environment of cells are often opaque. Optical coherence tomography (OCT) is a noninvasive label-free imaging technique, which offers the potential to visualize moving cells on opaque surfaces and in three dimensions (3D). Here, we demonstrate that OCT is an effective means of time-lapse videomicroscopy of Dictyostelium cells undergoing 3D (2D+time) cell migration on nitrocellulose substrates and 4D (3D+time) chemotaxis within low-density agarose gels. The generated image sequences are compatible with current computer-based image-analysis software for quantification of cell motility. This demonstrates the utility of OCT for cell tracking and analysis of cell chemotaxis in complex environments. PMID- 19475628 TI - Epidemiological study of genotypes of hepatitis B virus in northern Portugal. AB - While the overall prevalence of hepatitis B virus (HBV) infection in Portugal is around 1%, there are no published studies examining HBV genotypes in this country. This study aimed to survey HBV genotypes in the northern Portugal and to examine the possible associations between genotypes and gender, viral transmission routes, viral markers, viral load, and biochemical tests of liver function. The study sample consists of 340 patients with HBV infection of whom 42.9% were women. Tests were carried out for HBV genotypes and biochemical liver function while demographic information, including alcohol intake, was obtained from the patient files. The results indicate the predominance of genotype D (60.3%) and genotype A (31.5%). Intrafamilial transmission was predominant in female patients, while males were infected in equal proportions by perinatal, sexual, and intrafamilial transmission. Absence of HBeAg was found in a significantly smaller proportion of female patients with genotype D as compared to A (56.6% vs. 82.1%, P = 0.028). High viral load was associated significantly and independently with genotype D and HBeAg. Both alanine and aspartate aminotransferases (ALT and AST) were associated with gender and HBeAg. Thus, genotypes A and D were found to be the most prevalent in the north of Portugal. Patients infected with genotype D had higher levels of HBV DNA. HBeAg was associated with genotype D, viral load, and ALT and AST. PMID- 19475629 TI - A comparative study of the frequency of antibody and titers against human herpesvirus 8 latent and lytic antigens in "at-risk" individuals and among patients with Kaposi's sarcoma. AB - Differences in the prevalence of human herpesvirus 8 (HHV-8) and Kaposi's sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross- sectional study aimed at detecting the frequency and titers of antibodies against HHV-8 latent and lytic antigens in serum samples from individuals with different risk-factors for HHV-8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV-8-specific antibodies to latent and lytic antigens using "in house" immunofluorescence assays. The results were analyzed by the Chi-square, Fisher's exact test, Kruskal-Wallis and/or Mann-Whitney U-tests. The frequencies of HHV-8 antibodies were as follows: 87.5-100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different "at-risk" populations for HHV-8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high-risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS. PMID- 19475630 TI - Effects of acute ultra-low dose mecamylamine on cognition in adult attention deficit/hyperactivity disorder (ADHD). AB - OBJECTIVE: Nicotinic cholinergic stimulation has known beneficial effects in attention-deficit/hyperactivity disorder (ADHD). Mecamylamine is a non competitive nicotinic antagonist which is reported in several animal studies to have paradoxical positive effects on cognition at ultra-low doses. Comparable studies in humans have not been conducted. The aim of this study was to determine the effects of acute ultra-low doses of mecamylamine on cognition in adult ADHD. METHODS: Fifteen (6 female) non-smokers with ADHD completed this acute, within subjects, double blind study of 0.2, 0.5, 1.0 mg of oral mecamylamine and placebo. Behavioral inhibition, recognition memory, and delay aversion were assessed at each dose. RESULTS: The 0.5 mg dose of mecamylamine significantly improved recognition memory and reduced tolerance for delay. Mecamylamine increased participant rated irritability and investigator rated restlessness. There were no effects on vital signs or physical side effects. CONCLUSION: This is the first study to find measurable effects of ultra-low doses of mecamylamine in humans. Mecamylamine did not improve core ADHD cognitive symptoms, but significantly improved recognition memory. These effects may represent mixed receptor activity (activation and blockade) at the doses tested. The finding of beneficial effects on memory processes has important clinical implications and further exploration of this effect is warranted. PMID- 19475632 TI - Force field dependence of phospholipid headgroup and acyl chain properties: comparative molecular dynamics simulations of DMPC bilayers. AB - The reliability of molecular simulations largely depends on the quality of the empirical force field parameters. Force fields used in lipid simulations continue to be improved to enhance the agreement with experiments for a number of different properties. In this work, we have carried out molecular dynamics simulations of neat DMPC bilayers using united-atom Berger force field and three versions of all-atom CHARMM force fields. Three different systems consisting of 48, 72, and 96 lipids were studied. Both particle mesh Ewald (PME) and spherical cut-off schemes were used to evaluate the long-range electrostatic interactions. In total, 21 simulations were carried out and analyzed to find out the dependence of lipid properties on force fields, system size, and schemes to calculate long range interactions. The acyl chain order parameters calculated from Berger and the recent versions of CHARMM simulations have shown generally good agreement with the experimental results. However, both sets of force fields deviate significantly from the experimentally observed P-C dipolar coupling values for the carbon atoms that link the choline and glycerol groups with the phosphate groups. Significant differences are also observed in several headgroup parameters between CHARMM and Berger simulations. Our results demonstrate that when changes were introduced to improve CHARMM force field using PME scheme, all the headgroup parameters have not been reoptimized. The headgroup properties are likely to play a significant role in lipid-lipid, protein-lipid, and ligand-lipid interactions and hence headgroup parameters in phospholipids require refinement for both Berger and CHARMM force fields. PMID- 19475633 TI - Molecular dynamics simulation study of association in trifluoroethanol/water mixtures. AB - Mixtures of Trifluoroethanol (TFE) and water with different proportions are studied using molecular dynamics simulations. The radial and spatial distribution functions, as well as the size distribution of TFE clusters are obtained from the trajectories. The variation of radial and spatial distribution functions with composition show that the addition of TFE enhances the water structure, but the hydrogen bonds between TFE molecules are broken as TFE is diluted with water. The TFE-rich solutions have stronger TFE-water hydrogen bonds. The clustering of TFE molecules in low concentration region is attributed to the hydrophobic interactions between CF(3) groups. The distribution of cluster sizes in solution supports these conclusions. PMID- 19475634 TI - Evidence for epistasis between SLC6A4 and a chromosome 4 gene as risk factors in major depression. AB - Linkage analysis on Utah pedigrees with strong family histories of major depression including only cases with the SLC6A4 HTTLPR short allele revealed a linkage peak on chromosome 4 (maximum HLOD = 3.5). This evidence suggests epistasis between SLC6A4 and an unknown gene as risk factors for major depression. PMID- 19475635 TI - Drop-out from treatment for the eating disorders: a problem for clinicians and researchers. AB - All professionals who work in the field of eating disorders will have encountered patients who do not make it into or through a course of treatment. This paper considers some of the difficulties that drop-out poses to clinicians and researchers. It also suggests strategies for addressing these challenges in future research and clinical practice. PMID- 19475631 TI - Non-replication of association for six polymorphisms from meta-analysis of genome wide association studies of Parkinson's disease: large-scale collaborative study. AB - Early genome-wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta-analysis of the first two GWA investigations might be replicable in different populations. We examined six single-nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the "Genetic Epidemiology of Parkinson's Disease" (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixed and random effects models. The summary allelic odds ratios were ranging from 0.97 to 1.09 by random effects, when all data were included. The summary estimates of the replication data sets (excluding the original GWA data) were very close to 1.00 (range 0.98-1.09) and none of the effects were nominally statistically significant. The replication data sets had significantly different results than the GWA data. Our data do not support evidence that any of these six SNPs reflect susceptibility markers for PD. Much stronger signals of statistical significance in GWA platforms are needed to have substantial chances of replication. Specifically in PD genetics, this would require much larger GWA studies and perhaps novel analytical techniques. PMID- 19475636 TI - Theory of long-range diffusion of proteins on a spherical biological membrane: application to protein cluster formation and actin-comet tail growth. AB - Breaking of symmetry is often required in biology in order to produce a specific function. In this work we address the problem of protein diffusion over a spherical vesicle surface towards one pole of the vesicle in order to produce ultimately an active protein cluster performing a specific biological function. Such a process is, for example, prerequisite for the assembling of proteins which then cooperatively catalyze the polymerization of actin monomers to sustain the growth of actin tails as occurs in natural vesicles such as those contained in Xenopus eggs. By this process such vesicles may propel themselves within the cell by the principle of action-reaction. In this work the physicochemical treatment of diffusion of large biomolecules within a cellular membrane is extended to encompass the case when proteins may be transiently poised by corral-like structures partitioning the membrane as has been recently documented in the literature. In such case the exchange of proteins between adjacent corrals occurs by energy-gated transitions instead of classical Brownian motion, yet the present analysis shows that long-range movements of the biomolecules may still be described by a classical diffusion law though the diffusion coefficient has then a different physical meaning. Such a model explains why otherwise classical diffusion of proteins may give rise to too small diffusion coefficients compared to predictions based on the protein dimension. This model is implemented to examine the rate of proteins clustering at one pole of a spherical vesicle and its outcome is discussed in relevance to the mechanism of actin comet tails growth. PMID- 19475637 TI - Force spectroscopy of the interaction between mycobacterial adhesins and heparan sulphate proteoglycan receptors. AB - Understanding the molecular interactions between bacterial adhesion proteins (adhesins) and their receptors is essential for elucidating the molecular mechanisms of bacterial pathogenesis. Here, atomic force microscopy (AFM) is used to explore the specific interactions between the heparin-binding hemagglutinin (HBHA) from Mycobacterium tuberculosis, and heparan sulphate proteoglycan (HSPG) receptors on live A549 pneumocytes. First, we show that the specific binding forces between single HBHA-HSPG pairs, 57+/-16 pN, are similar to the forces measured earlier between HBHA and heparin molecules. Second, we mapped the distribution of single HSPG receptors on the surface of A549 cells, revealing that the proteins are widely and homogeneously exposed. Third, we observed force curves with constant force plateaus at large pulling velocities, reflecting the extraction of membrane tethers or nanotubes. These single-molecule measurements provide new avenues in pathogenesis research, particularly for elucidating the molecular basis of pathogen-host interactions. PMID- 19475638 TI - Fluorescence quenching by photoinduced electron transfer: a reporter for conformational dynamics of macromolecules. AB - Photoinduced electron transfer (PET) between organic fluorophores and suitable electron donating moieties, for example, the amino acid tryptophan or the nucleobase guanine, can quench fluorescence upon van der Waals contact and thus report on molecular contact. PET-quenching has been used as reporter for monitoring conformational dynamics in polypeptides, proteins, and oligonucleotides. Whereas dynamic quenching transiently influences quantum yield and fluorescence lifetime of the fluorophore, static quenching in pi-stacked complexes efficiently suppresses fluorescence emission over time scales longer than the fluorescence lifetime. Static quenching therefore provides sufficient contrast to be observed at the single-molecule level. Here, we review complex formation and static quenching of different fluorophores by various molecular compounds, discuss applications as reporter system for macromolecular dynamics, and give illustrating examples. PMID- 19475639 TI - Discovery of selective luteinizing hormone receptor agonists using the bivalent ligand method. AB - Two series of dimeric ligands for a G-protein-coupled receptor were prepared that differ by the interconnecting spacer system. Biological evaluation revealed that both dimeric series exhibit unique biological properties relative to their monomeric counterparts.The luteinizing hormone receptor (LHR), the follicle stimulating hormone receptor (FSHR), and the thyroid-stimulating hormone receptor (TSHR) belong to the glycoprotein hormone receptor (GpHR) family. A prominent feature of all endogenous glycoprotein ligands is that they share an identical alpha subunit and acquire their selectivity from the unique beta subunit. Recent developments in pro-fertility research have led to the discovery of several low molecular-weight agonists for the luteinizing hormone/choriogonadotropin receptor that bind to the transmembrane (TM) region of the LHR. Interestingly, some of these agonists are also able to activate the FSHR. Several research groups have shown that ligand dimerization presents a powerful tool to increase the subtype selectivity for structurally related G-protein-coupled receptors. In this work, we applied the dimerization strategy to GpHRs and explored the effect on receptors with closely related TM regions. Two series of dimeric ligands were prepared that differ in the interconnecting spacer system. Biological evaluation revealed that both series exhibit unique selectivity properties for the LHR, originating from either decreased potency or a decreased efficacy toward the FSHR. PMID- 19475641 TI - Dutch training and research in forensic psychiatry in a European perspective. PMID- 19475642 TI - Quality of life issues following surgery for vulval cancer: a case report. AB - BACKGROUND AND PURPOSE: Surgical intervention for vulvar cancer and vulvar intraepithelial neoplasia causes mutilation of the genital area and can impose significant bladder, bowel and sexual dysfunction. This case report outlines how conservative interventions such as pelvic floor muscle training (PFMT) may reduce the long-term morbidities of such dysfunction. METHOD: The patient underwent 16 weeks of PFMT in conjunction with advice on fluid intake and bladder training. RESULTS: An increase in pelvic floor muscle strength and endurance were recorded. Improved bladder control as demonstrated by a reduction in frequency of voiding (from 15 to 7 per 24 hours), and number of pads used (from 6 to 3 per 24 hours) was evident. The impact of urinary incontinence on everyday life was much less at the end of the treatment period as measured by the Incontinence Impact Questionnaire with a change in score from 21 (maximum impact) to 10. CONCLUSIONS: These positive results indicate that further research is needed to investigate the effect of PFMT on bladder function following such surgery. PMID- 19475640 TI - Serum adiponectin, C-peptide and leptin and risk of symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial. AB - BACKGROUND: Recent epidemiologic studies have identified obesity as a risk factor for benign prostatic hyperplasia (BPH). We examined whether adiponectin, leptin, and C-peptide were associated with incident, symptomatic BPH and whether these factors mediate the relationship between obesity and BPH risk. METHODS: Data are from Prostate Cancer Prevention Trial placebo arm participants who were free of BPH at baseline. Incident BPH (n = 698) was defined as treatment, two International Prostate Symptom Score (IPSS) values > 14, or an increase of >or=5 in IPSS from baseline documented on at least two occasions plus at least one score >or=12. Controls (n = 709) were selected from men reporting no BPH treatment or IPSS > 7 during the 7-year trial. Baseline serum was analyzed for adiponectin, C-peptide, and leptin concentrations. RESULTS: Neither C-peptide nor leptin was associated with BPH risk. The odds ratio [95% CI] contrasting highest to lowest quartiles of adiponectin was 0.65[0.47, 0.87] P(trend) = 0.004. Findings differed between levels of physical activity: there was a strong inverse association between adiponectin and BPH among moderately/very active men OR = 0.43 [0.29, 0.63], and no association among sedentary/minimally active men OR = 0.92 [0.65, 1.30] P(interaction) = 0.005. Adiponectin concentrations explained only a moderate amount of the relationship between obesity and BPH risk. CONCLUSIONS: High adiponectin concentrations were associated with reduced risk of incident, symptomatic BPH. This association was limited to moderately/very active men; suggesting the relationship between obesity and BPH involves a complex interaction between factors affecting glucose uptake and insulin sensitivity. However, adiponectin is likely not the only mechanism through which obesity affects BPH risk. PMID- 19475644 TI - Nanoparticle one-dimensional photonic-crystal dye laser. PMID- 19475643 TI - Prognostic value of modeled PSA clearance on biochemical relapse free survival after radical prostatectomy. AB - PURPOSES: Using population kinetic approach, we modeled PSA decline equations in patients with prostate cancer after radical prostatectomy (RP). We looked for relationships between early PSA decrease profile, characterized by PSA clearance (CL(PSA)) or half-life (HL(PSA)), and the 2-year biochemical relapse free survival (bRFS). PATIENTS AND METHODS: We performed a retrospective study on 55 patients treated with RP and with at least 2 PSA measurements in the post operative month. A population kinetic model was investigated with NONMEM. The prognostic factors regarding bRFS were assessed using univariate and multivariate analyses. RESULTS: The best model describing the PSA post-operative decrease was bi-compartmental and fit patient data well. Median CL(PSA) was 0.034 (terciles were 0.023 and 0.048). The significant prognostic factors associated with a better bRFS with univariate analysis were lower CL(PSA) terciles (2-year bRFS = 100% vs. 85.1% vs. 66.7% if CL(PSA) < 0.023, 0.023 or= 0.0480, P = 0.006) as well as initial PSA < 7 ng/ml, pT2 stage (vs. pT3), pN0 (vs. pN1) and low main Gleason score (3/5 vs. 4/5). Among these factors, CL(PSA) was the only independent prognostic factor with multivariate analysis regarding bRFS (HR = 0.92, 95%CI = [0.86-0.98], P = 0.0088). CONCLUSION: CL(PSA) determined with 4 PSA concentrations in the first month following the RP may predict the biochemical relapse risk of prostate cancer patients, thus enabling early identification of high-risk patients requiring adjuvant treatment. A prospective validation of these results is required. PMID- 19475645 TI - Social and emotional detachment: a cross-cultural comparison of the non disruptive behavioural psychopathic traits in children. AB - BACKGROUND: Questions about the international reliability and validity of aspects of psychopathy have been raised for adults, but hardly considered when applying the constructs to children. AIMS/OBJECTIVES: Our aim was to compare the psychometrics of a new instrument to measure psychopathic traits in children between two countries - the Netherlands and Greece. We also tested the hypothesis that, in both countries, both narcissistic-egocentric and callous-unemotional dimensions would be related to observed behavioural disorders. METHODS: The Social and Emotional Detachment Questionnaire was used to assess narcissistic egocentric and callous-unemotional dimensions of personality in representative national and community samples of 4-12-year-old children in the Netherlands and Greece, respectively. Parents filled in the questionnaires anonymously and also provided ratings of conduct disorders. RESULTS: A two-dimensional construct of the psychopathic syndrome depicting, respectively, narcissistic and unemotional traits was reliable and valid in both countries, although there was considerable correlation between these two dimensions, which we designated 'social detachment' and 'emotional detachment', respectively. In both countries, the composite of social and emotional detachment was associated with aggressive and antisocial conduct disorders. CONCLUSIONS/IMPLICATIONS: The reliability, validity and predictive value of this questionnaire must be tested further, for example, through multiple informants and longitudinally, but our findings that the tool performs robustly in two very different European countries is encouraging in terms of its potential value as a clinical screening tool and a tool for furthering the understanding of serious behavioural disorders in children. PMID- 19475646 TI - Reactive oxygen species formation is not enhanced by exposure to UMTS 1950 MHz radiation and co-exposure to ferrous ions in Jurkat cells. AB - This study was designed to assess if radiofrequency (RF) radiation induces oxidative stress in cultured mammalian cells when given alone or in combination with ferrous ions (FeSO(4)). For this purpose the production of reactive oxygen species (ROS) was measured by flow cytometry in human lymphoblastoid cells exposed to 1950 MHz signal used by the third generation wireless technology of the Universal Mobile Telecommunication System (UMTS) at Specific Absorption Rate of 0.5 and 2.0 W/kg. Short (5-60 min) or long (24 h) duration exposures were carried out in a waveguide system under strictly controlled conditions of both dosimetry and environment. Cell viability was also measured after 24 h RF exposure using the Resazurin and Neutral Red assays. Several co-exposure protocols were applied to test if RF radiation is able to alter ROS formation induced by FeSO(4) (RF given before or concurrently to FeSO(4)). The results obtained indicate that non-thermal RF exposures do not increase spontaneous ROS formation in any of the experimental conditions investigated. Consistent with the lack of ROS production, no change in cell viability was observed in Jurkat cells exposed to RF radiation for 24 h. Similar results were obtained when co-exposures were considered: combined exposures to RF radiation and FeSO(4) did not increase ROS formation induced by the chemical treatment alone. In contrast, in cultures treated with FeSO(4) as positive control, a dose-dependent increase in ROS formation was recorded, validating the sensitivity of the method employed. PMID- 19475647 TI - Short-term exposure to mobile phone base station signals does not affect cognitive functioning or physiological measures in individuals who report sensitivity to electromagnetic fields and controls. AB - Individuals who report sensitivity to electromagnetic fields often report cognitive impairments that they believe are due to exposure to mobile phone technology. Previous research in this area has revealed mixed results, however, with the majority of research only testing control individuals. Two studies using control and self-reported sensitive participants found inconsistent effects of mobile phone base stations on cognitive functioning. The aim of the present study was to clarify whether short-term (50 min) exposure at 10 mW/m(2) to typical Global System for Mobile Communication (GSM) and Universal Mobile Telecommunications System (UMTS) base station signals affects attention, memory, and physiological endpoints in sensitive and control participants. Data from 44 sensitive and 44 matched-control participants who performed the digit symbol substitution task (DSST), digit span task (DS), and a mental arithmetic task (MA), while being exposed to GSM, UMTS, and sham signals under double-blind conditions were analyzed. Overall, cognitive functioning was not affected by short-term exposure to either GSM or UMTS signals in the current study. Nor did exposure affect the physiological measurements of blood volume pulse (BVP), heart rate (HR), and skin conductance (SC) that were taken while participants performed the cognitive tasks. PMID- 19475648 TI - Effects of W-CDMA 1950 MHz EMF emitted by mobile phones on regional cerebral blood flow in humans. AB - Use of the third generation mobile phone system is increasing worldwide. This is the first study to investigate the effects of the third generation system on regional cerebral blood flow (rCBF) in humans. We compared effects of the electromagnetic field (EMF) emitted from the Wideband Code Division Multiple Access (W-CDMA) cellular system versus sham control exposure on rCBF in humans. Nine healthy male volunteers participated in this study. Positron emission tomography (PET) scans were obtained before, during, and after unilateral 30 min EMF exposure. The subtraction analysis revealed no significant rCBF changes caused by the EMF conditions compared with the sham exposure, suggesting that EMF emitted by a third generation mobile phone does not affect rCBF in humans. PMID- 19475649 TI - IP(3) mobilization and diffusion determine the timing window of Ca(2+) release by synaptic stimulation and a spike in rat CA1 pyramidal cells. AB - Synaptically activated calcium release from internal stores in CA1 pyramidal neurons is generated via metabotropic glutamate receptors by mobilizing IP(3). Ca(2+) release spreads as a large amplitude wave in a restricted region of the apical dendrites of these cells. These Ca(2+) waves have been shown to induce certain forms of synaptic potentiation and have been hypothesized to affect other forms of plasticity. Pairing a single backpropagating action potential (bAP) with repetitive synaptic stimulation evokes Ca(2+) release when synaptic stimulation alone is subthreshold for generating release. We examined the timing window for this synergistic effect under conditions favoring Ca(2+) release. The window, measured from the end of the train, lasted 250-500 ms depending on the duration of stimulation tetanus. The window appears to correspond to the time when both IP(3) concentration and [Ca(2+)](i) are elevated at the site of the IP(3) receptor. Detailed analysis of the mechanisms determining the duration of the window, including experiments using different forms of caged IP(3) instead of synaptic stimulation, suggest that the most significant processes are the time for IP(3) to diffuse away from the site of generation and the time course of IP(3) production initiated by activation of mGluRs. IP(3) breakdown, desensitization of the IP(3) receptor, and the kinetics of IP(3) unbinding from the receptor may affect the duration of the window but are less significant. The timing window is short but does not appear to be short enough to suggest that this form of coincidence detection contributes to conventional spike timing dependent synaptic plasticity in these cells. PMID- 19475650 TI - Progesterone promotes the survival of newborn neurons in the dentate gyrus of adult male mice. AB - This study investigated the effects of progesterone (P4) on the production and survival of neurons in the hippocampal dentate gyrus of adult male mice. The administration of P4 (4 mg/kg) for 3 consecutive days beginning on the 0-2nd day after the first BrdU-injection (BrdU-D(0-2)) produced an approximately twofold increase in the number of 28- and 56-day-old BrdU(+) cells in comparison to the controls, whereas it did not alter the number of 24/48-h-old BrdU(+) cells. P4 preferentially promoted the survival of newborn neurons when administered at BrdU D(5-7), but not at BrdU-D(10-12) and BrdU-D(15-17). Androstenedione (Ad), testosterone (TE), or estradiol (E2) at the same-dose of P4, when administered at BrdU-D(0-2), could not replicate the effect of P4, while the inhibition of 5alpha reductase by finasteride did not affect the P4-action, indicating that the P4 effect is exerted by P4 itself but not by its metabolites. On the other hand, the P4R antagonist RU486 partially suppressed the P4-effect, while inhibitors for Src, MEK, or PI3K totally suppressed the P4-effect. Finally, the P4-enhanced survival of newborn neurons was accompanied by a potentiation of spatial learning and memory, which was P4R-dependent. These findings suggest that P4 enhances the survival of newborn neurons through P4R and/or the Src-ERK and PI3K pathways independent of its influence on cell proliferation, which is well correlated with the potentiated spatial cognitive function of P4-treated animals. PMID- 19475651 TI - Modulatory metaplasticity induced by pregnenolone sulfate in the rat hippocampus: a leftward shift in LTP/LTD-frequency curve. AB - We recently have found that an acute application of the neurosteroid pregnenolone sulfate (PREGS) at 50 muM to rat hippocampal slices induces a long-lasting potentiation (LLP(PREGS)) via a sustained ERK2/CREB activation at perforant path/granule-cell synapses in the dentate gyrus. This study is a follow up to investigate whether the expression of LLP(PREGS) influences subsequent frequency dependent synaptic plasticity. Conditioning electric stimuli (CS) at 0.1-200 Hz were given to the perforant-path of rat hippocampal slices expressing LLP(PREGS) to induce long-term potentiation (LTP) and long-term depression (LTD). The largest LTP was induced at about 20 Hz-CS, which is normally a subthreshold frequency, and the largest LTD at 0.5 Hz-CS, resulting in a leftward-shift of the LTP/LTD-frequency curve. Furthermore, the level of LTP at 100 Hz-CS was significantly attenuated to give band-pass filter characteristics of LTP induction with a center frequency of about 20 Hz. The LTP induced by 20 Hz-CS (termed 20 Hz-LTP) was found to be postsynaptic origin and dependent on L-type voltage-gated calcium channel (L-VGCC) but not on N-methyl-D-aspartate receptor (NMDAr). Moreover, the induction of 20 Hz-LTP required a sustained activation of ERK2 that had been triggered by PREGS. In conclusion, the transient elevation of PREGS is suggested to induce a modulatory metaplasticity through a sustained activation of ERK2 in an L-VGCC dependent manner. PMID- 19475653 TI - Light deprivation improves melatonin related suppression of hippocampal plasticity. AB - In early postnatal life, sensory inputs deeply influence development as well as function of the brain. Plasticity of synaptic transmission including its experimentally induced form, long-term potentiation (LTP), is affected by sensory deprivation in neocortex. This study is devoted to assess if dark rearing and a dark phase synthesized hormone melatonin influence LTP in the hippocampus, an area of brain involved in learning and memory. In vivo experiments were carried out on two groups of 45-days-old male Wistar rats kept in standard 12-h light/dark condition [light reared (LR) tested during the light phase] or in complete darkness [dark reared (DR)] since birth to testing. Each group, in turn, was divided to two, vehicle- and melatonin-treated, groups. Stimulating the Schaffer collaterals of CA3 area of hippocampus extracellular postsynaptic potentials (EPSPs) were recorded in the CA1 area. Having the stable baseline responses to the test pulses, the hippocampus was perfused by either vehicle or 2 microg melatonin and EPSPs were recorded for 30 min. Then, for induction of LTP, the tetanus was applied to the Schaffer collaterals and the field potentials were pooled for 120-min post-tetanus. The light deprivation resulted in a significant augmentation in the amplitude of baseline responses. Also, we observed a melatonin-induced increase in amplitude of the baseline recordings in either LR or DR animals. Tetanic stimulation elicited LTP of EPSPs in both LR and DR groups, robustly in the former where it lasted for about 90 min. Generally, melatonin inhibited the production of LTP in the two groups especially in the LR animals leading to a noticeable depression. We concluded that higher level of neuronal activity in the DR rats gives rise to a lower level of LTP. Weaker effect of melatonin on blocking the potentiation of post-tetanus EPSPs in the DR rats may be the result of a desensitization of melatonin receptors due to chronically increased levels of this hormone in the visually deprived rats. PMID- 19475652 TI - Fornix transection selectively impairs fast learning of conditional visuospatial discriminations. AB - As the fornix has previously been implicated in the rapid learning of associations, we hypothesized that fornix transection in macaques would selectively impair the acquisition of rapidly learned conditional visuospatial discrimination problems. Macaque monkeys learned, postoperatively, three sets of concurrent problems of increasing sizes containing 8, 32, and 64 problems, respectively. Each problem consisted of four identical visual stimuli and animals had to learn which stimulus position was rewarded. The lesioned animals made significantly more errors-to-criterion on the smallest set of problems, consistent with the idea that the most rapidly acquired sets would be more vulnerable to fornical damage. Moreover, during the early stages of acquisition across all three sets, fornix transection selectively impeded monkeys' abilities to eliminate nonperseverative errors in correction trials, consistent with an inability to monitor or correct erroneous spatial responses made further back in time than the last trial. Both one-trial learning and an errorless learning (facilitation of performance) were observed in control and fornix lesioned animals but neither were fornix-dependent and overcoming the deleterious effect upon subsequent learning of having made prior errors was also unaffected by fornix transection. The data indicate that the fornix is not important for all forms of new learning; rather it is selectively concerned with the relatively rapid acquisition of spatial and temporal relationships between stimuli and responses. PMID- 19475654 TI - Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A(2)beta in prostate cancer cells. AB - BACKGROUND: Serum prostate specific antigen (PSA) levels in prostate cancer patients serve as a useful biomarker for diagnosing and monitoring prostate cancer. Recently, secreted PSA has been characterized as an autocrine survival factor through activation of Akt and induction of AR. In the normal prostate, PSA is secreted in the lumen of prostatic ducts to lyse proteins in the seminal coagulum. METHODS: However, the mechanism for constitutive PSA secretion from benign prostate and its transport across the prostate-blood barrier into serum are unknown. Regulation of peptide secretion by iPLA(2)-beta has been reported in non-prostatic tissue and in prostate tissue iPLA(2)-beta is reported to be under androgen regulation. We investigated whether iPLA(2) plays a role for in PSA secretion by comparing iPLA(2) activity and expression in normal prostate epithelial RWPE-1 cells and in LNCaP prostate cancer cells. Expression of the two active iPLA(2)-beta mRNA splice variants, LH-iPLA(2) and SH-iPLA(2), were increased and the inhibitory ankyrin-iPLA(2) isoform was markedly reduced in LNCaP cells as compared to normal prostate epithelial RWPE-1 cells. RESULTS: These changes are consistent with a higher enzymatic activity in LNCaP cells. The iPLA(2)-beta-specific inhibitor BEL inhibited PSA secretion and induced apoptosis in LNCaP cells. iPLA(2) knockdown using SiRNA inhibited PSA secretion, downregulated AR and induced apoptosis. Exogenous PSA suppressed BEL-induced apoptosis and neutralizing anti-PSA antibody blocked the survival effect of PSA. CONCLUSIONS: These data indicate that iPLA(2)-beta participates in regulating PSA secretion and supports the concept that secreted PSA provides an autocrine survival function in LNCaP cells. PMID- 19475655 TI - Autophonia in anorexia nervosa. AB - OBJECTIVE: To increase awareness among clinicians treating otolaryngologic symptoms in very low weight anorexic patients. METHOD: Focused clinical examination on admission and regular physical assessments during in-patient stay was conducted and symptoms compared with other in-patients on the eating disorders unit. RESULTS: Notable improvement in otolaryngological symptoms on gaining weight. DISCUSSION: Ward based clinical examination revealed a normal tympanic membrane in our very low weight anorexic patients. Our results emphasise the possibility of loss of fatty tissue surrounding the Eustachian tube to be the primary cause for their otolaryngological symptoms. We have attempted to increase awareness among clinicians treating anorexic patients with similar symptoms. PMID- 19475657 TI - 2009 Ebert Prize. Editorial. PMID- 19475656 TI - Screening for generalized anxiety disorder symptoms in the wake of terrorist attacks: a study in primary care. AB - Little is known about the mental health impact of terrorism beyond posttraumatic stress disorder (PTSD) and depression. The associations between exposure to the September 11, 2001 (9/11) attacks in New York City and generalized anxiety disorder (GAD) symptoms were examined in a sample of 929 primary care patients. After controlling for PTSD, depression, panic and substance use disorders, and pre-9/11 trauma, patients who screened positive (vs. negative) for GAD symptoms were roughly twice as likely to report having a loved one at the 9/11 disaster site, twice as likely to know someone who was killed by the attacks, and twice as likely to know someone who was involved with the rescue/recovery efforts after the disaster. Implications for treatment and future research are discussed. PMID- 19475658 TI - Dopamine modulation of the in vivo acetylcholine response in the Drosophila mushroom body. AB - Olfactory sensory information in Drosophila is transmitted through antennal lobe projections to Mushroom Body neurons (Kenyon cells) by means of cholinergic synapses. Application of acetylcholine (ACh) and odors produce significant increases in intracellular calcium ([Ca(2+)](i)) in these neurons. Behavioral studies show that Kenyon cell activity is modulated by dopaminergic inputs and this modulation is thought to be the basis for an olfactory conditioned response. However, quantitative assessment of the synaptic inputs to Kenyon cells is currently lacking. To assess neuronal activity under in vivo conditions, we have used the endogenously-expressed camgaroo reporter to measure [Ca(2+)](i) in these neurons. We report here the dose-response relationship of Kenyon cells for ACh and dopamine (DA). Importantly, we also show that simultaneous application of ACh and DA results in a significant decrease in the response to ACh alone. In addition, we show inhibition of the ACh response by cyclic adenosine monophosphate. This is the first quantitative assessment of the effects of these two important transmitters in this system, and it provides an important basis for future analysis of the cellular mechanisms of this well established model for associative olfactory learning. PMID- 19475659 TI - Decreased ventilatory response to hypercapnia in dementia with Lewy bodies. AB - A systematic autonomic dysfunction observed among patients with dementia with Lewy bodies (DLB) has recently attracted close attention. Here, we compare cardiovascular and pulmonary autonomic functions among patients with DLB, patients with Alzheimer's disease, and healthy control subjects. All 15 DLB patients demonstrated severely low ventilatory response to hypercapnia, whereas none of the other subjects demonstrated abnormal results. The majority of the DLB patients showed impaired heart rate variability, low uptake on (123)I metaiodobenzylguanidine myocardial scintigraphy, and orthostatic hypotension. Ventilatory response to hypercapnia as a marker of respiratory autonomic function is a promising diagnostic tool for DLB. PMID- 19475660 TI - Basal ganglia pathophysiology in Parkinson's disease. PMID- 19475662 TI - What sort of change to believe in: an alternate opinion. PMID- 19475663 TI - Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process. AB - Islet Amyloid Polypeptide (IAPP or amylin) is a peptide hormone produced and stored in the beta-islet cells of the pancreas along with insulin. IAPP readily forms amyloid fibrils in vitro, and the deposition of fibrillar IAPP has been correlated with the pathology of type II diabetes. The mechanism of the conversion that IAPP undergoes from soluble to fibrillar forms has been unclear. By chaperoning IAPP through fusion to maltose binding protein, we find that IAPP can adopt a alpha-helical structure at residues 8-18 and 22-27 and that molecules of IAPP dimerize. Mutational analysis suggests that this dimerization is on the pathway to fibrillation. The structure suggests how IAPP may heterodimerize with insulin, which we confirmed by protein crosslinking. Taken together, these experiments suggest the helical dimerization of IAPP accelerates fibril formation and that insulin impedes fibrillation by blocking the IAPP dimerization interface. PMID- 19475664 TI - Mistic: cellular localization, solution behavior, polymerization, and fibril formation. AB - Mistic represents a family of unique membrane-associating proteins originally found in Bacillus subtilis (M110). As a fusion partner, it has been shown to assist overexpression of foreign integral membrane proteins in E. coli. We have expressed shorter Mistic homologs from other Bacillus species and surprisingly, unlike M110, found them abundant in the cytoplasm. These Mistic homologs including the corresponding shorter sequence (amino acids 27 through 110 of M110) exist as multimeric assemblies in solution in the absence of detergent. Crystals of Mistic from B. leicheniformis (M2) diffracted to 3.2 A resolution, indicating that it exists as a multimer in the crystalline state as well. Moreover, we show that although M2 is mostly alpha-helical, it tends to polymerize and form fibrils. Such oligomerization could potentially mask the charged surface of the monomeric Mistic to assist membrane integration. PMID- 19475665 TI - Charge neutralization and collapse of the C-terminal tail of alpha-synuclein at low pH. AB - Alpha-synuclein (alphaS) is the primary component of Lewy bodies, the pathological hallmark of Parkinson's Disease. Aggregation of alphaS is thought to proceed from a primarily disordered state with nascent secondary structure through intermediate conformations to oligomeric forms and finally to mature amyloid fibrils. Low pH conditions lead to conformational changes associated with increased alphaS fibril formation. Here we characterize these structural and dynamic changes using solution state NMR measurements of secondary chemical shifts, relaxation parameters, residual dipolar couplings, and paramagnetic relaxation enhancement. We find that the neutralization of negatively charged side-chains eliminates electrostatic repulsion in the C-terminal tail of alphaS and leads to a collapse of this region at low pH. Hydrophobic contacts between the compact C-terminal tail and the NAC (non-amyloid-beta component) region are maintained and may lead to the formation of a globular domain. Transient long range contacts between the C-terminus of the protein and regions N-terminal to the NAC region are also preserved. Thus, the release of long-range contacts does not play a role in the increased aggregation of alphaS at low pH, which we instead attribute to the increased hydrophobicity of the protein. PMID- 19475666 TI - Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia. AB - OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled, parallel group study of both memantine and constraint-induced aphasia therapy (CIAT) on chronic poststroke aphasia followed by an open-label extension phase. METHODS: Patients were randomized to memantine (20 mg/day) or placebo alone during 16 weeks, followed by combined drug treatment with CIAT (weeks 16-18), drug treatment alone (weeks 18-20), and washout (weeks 20-24), and finally, an open label extension phase of memantine (weeks 24-48). After baseline evaluations, clinical assessments were done at two end points (weeks 16 and 18), and at weeks 20, 24, and 48. Outcome measures were changes in the Western Aphasia Battery Aphasia Quotient and the Communicative Activity Log. RESULTS: Twenty-eight patients were included, and 27 completed both treatment phases. The memantine group showed significantly better improvement on Western Aphasia Battery-Aphasia Quotient compared with the placebo group while the drug was taken (week 16, p = 0.002; week 18, p = 0.0001; week 20, p = 0.005) and at the washout assessment (p = 0.041). A significant increase in Communicative Activity Log was found in favor of memantine-CIAT relative to placebo-CIAT (week 18, p = 0.040). CIAT treatment led to significant improvement in both groups (p = 0.001), which was even greater under additional memantine treatment (p = 0.038). Beneficial effects of memantine were maintained in the long-term follow-up evaluation, and patients who switched to memantine from placebo experienced a benefit (p = 0.02). INTERPRETATION: Both memantine and CIAT alone improved aphasia severity, but best outcomes were achieved combining memantine with CIAT. Beneficial effects of memantine and CIAT persisted on long-term follow-up. PMID- 19475668 TI - T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon beta. AB - OBJECTIVE: T-helper 1 (Th1) and Th17 lymphocytes are involved in experimental autoimmune encephalomyelitis, the model of multiple sclerosis (MS). We characterized the Th1/Th17 cell populations in peripheral blood (PB), their interferon (IFN) receptor expression sensitivity to IFN-beta in MS patients. METHODS: In 30 untreated patients with active MS (AMS) and 32 with inactive MS (IMS), and in 22 healthy subjects, we measured intracellular cytokine expression, interleukin-17-producing myelin basic protein-stimulated PB lymphocytes, surface IFN type I receptor chain1 (IFN-alphaR1) expression, IFN-beta-dependent signal transducer and activator of transcription 1 (STAT1) phosphorylation, and apoptosis of anti-CD3 monoclonal antibody-stimulated PB lymphocytes. RESULTS: Th17 cell percentage increased around sevenfold in AMS compared with IMS or healthy subjects, but there was no change in Th1 cells. Th17 cells in AMS were myelin basic protein specific. The longitudinal follow-up of 18 MS patients shifting between AMS and IMS showed that the percentage of Th17 but not Th1 cells always increased in AMS. IFN-alphaR1 expression, IFN-beta-induced STAT1 activation, and apoptosis were significantly greater in Th17 than Th1 cells. IFN alphaR1 expression and IFN-beta-dependent STAT1 activation progressively increased in vitro with a highly significant positive correlation only in developing Th17 but not in Th0 or Th1 cells. INTERPRETATION: Evidence that an expansion of peripheral Th17 cells, a Th subset that can infiltrate brain parenchyma and damage cells, is associated with disease activity in MS. The greater IFN-alphaR1 level expressed by Th17 compared with Th1 cells might make them a selective target for IFN-beta therapy. PMID- 19475667 TI - SNCA variants are associated with increased risk for multiple system atrophy. AB - To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed a candidate single nucleotide polymorphism (SNP) association study of the 384 most associated SNPs in a genome-wide association study of Parkinson's disease in 413 MSA cases and 3,974 control subjects. The 10 most significant SNPs were then replicated in additional 108 MSA cases and 537 controls. SNPs at the SNCA locus were significantly associated with risk for increased risk for the development of MSA (combined p = 5.5 x 10(-12); odds ratio 6.2) [corrected]. PMID- 19475669 TI - Glutathione peroxidase activity modulates recovery in the injured immature brain. AB - OBJECTIVE: Mice subjected to traumatic brain injury at postnatal day 21 show emerging cognitive deficits that coincide with hippocampal neuronal loss. Here we consider glutathione peroxidase (GPx) activity as a determinant of recovery in the injured immature brain. METHODS: Wild-type and transgenic (GPxTg) mice overexpressing GPx were subjected to traumatic brain injury or sham surgery at postnatal day 21. Animals were killed acutely (3 or 24 hours after injury) to assess oxidative stress and cell injury in the hippocampus or 4 months after injury after behavioral assessments. RESULTS: In the acutely injured brains, a reduction in oxidative stress markers including nitrotyrosine was seen in the injured GPxTg group relative to wild-type control mice. In contrast, cell injury, with marked vulnerability in the dentate gyrus, was apparent despite no differences between genotypes. Magnetic resonance imaging demonstrated an emerging cortical lesion during brain maturation that was also indistinguishable between injured genotypes. Stereological analyses of cortical volumes likewise confirmed no genotypic differences between injured groups. However, behavioral tests beginning 3 months after injury demonstrated improved spatial memory learning in the GPxTg group. Moreover, stereological analysis within hippocampal subregions demonstrated a significantly greater number of neurons within the dentate of the GPx group. INTERPRETATION: Our results implicate GPx in recovery of spatial memory after traumatic brain injury. This recovery may be attributed, in part, to a reduction in early oxidative stress and selective, long-term sparing of neurons in the dentate. PMID- 19475671 TI - Remission of epilepsy after two drug failures in children: a prospective study. AB - OBJECTIVE: Determine the probability of a more than 1-year remission after failure of a second drug in children prospectively followed from initial diagnosis of epilepsy and then from time of second drug failure. Identify prognostic factors for remission after second drug failure. METHODS: Of 613 children, 128 did not respond favorably to 2 drugs, had a trial of at least a third drug (median, 3), and were followed for more than 1 year (median, 10.1 years) since second drug failure. Product limit and proportional hazards techniques were used to analyze predictors of any 1-year remission (Rem1) and 1- and 3-year remission at last contact (Rem1/3-LC). RESULTS: Seventy-three patients (57%) had a remission. Repeated remissions and relapses were common. Only 48 (37.5%) achieved Rem1-LC and 28 (23%) Rem3-LC. Idiopathic epilepsy (Rem1: rate ratio [RR], 3.64, p < 0.0001; Rem1-LC: RR, 2.57, p = 0.008) and seizure frequency (Rem1: RR, 0.76, p = 0.003; Rem1-LC: RR, 0.82, p = 0.04 per increase in category) were the most robust predictors. Symptomatic cause was the only correlate of Rem3 LC. Remission before second drug failure did not predict remission after second drug failure. INTERPRETATION: Remission after second drug failure is common but often temporary. Children who have not responded to two appropriate drugs should be carefully evaluated to maximize therapy and possibly considered for more aggressive treatments. PMID- 19475670 TI - Amyloid imaging in mild cognitive impairment subtypes. AB - OBJECTIVE: We utilized the amyloid imaging ligand Pittsburgh Compound B (PiB) to determine the presence of Alzheimer's disease (AD) pathology in different mild cognitive impairment (MCI) subtypes and to relate increased PiB binding to other markers of early AD and longitudinal outcome. METHODS: Twenty-six patients with MCI (13 single-domain amnestic-MCI [a-MCI], 6 multidomain a-MCI, and 7 nonamnestic MCI) underwent PiB imaging. Twenty-three had clinical follow-up (21.2 +/- 16.0 [standard deviation] months) subsequent to their PiB scan. RESULTS: Using cutoffs established from a control cohort, we found that 14 (54%) patients had increased levels of PiB retention and were considered "amyloid-positive." All subtypes were associated with a significant proportion of amyloid-positive patients (6/13 single-domain a-MCI, 5/6 multidomain a-MCI, 3/7 nonamnestic MCI). There were no obvious differences in the distribution of PiB retention in the nonamnestic MCI group. Predictors of conversion to clinical AD in a-MCI, including poorer episodic memory, and medial temporal atrophy, were found in the amyloid-positive relative to amyloid-negative a-MCI patients. Longitudinal follow up demonstrated 5 of 13 amyloid-positive patients, but 0 of 10 amyloid-negative patients, converted to clinical AD. Further, 3 of 10 amyloid-negative patients "reverted to normal." INTERPRETATION: These data support the notion that amyloid positive patients are likely to have early AD, and that the use of amyloid imaging may have an important role in determining which patients are likely to benefit from disease-specific therapies. In addition, our data are consistent with longitudinal studies that suggest a significant percentage of all MCI subtypes will develop AD. PMID- 19475672 TI - Delayed treatment with a p53 inhibitor enhances recovery in stroke brain. AB - OBJECTIVE: Cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural progenitor cells (NPCs) in the subventricular zone (SVZ). Most of these new cells die shortly after injury. The purpose of this study was to examine a novel strategy for treatment of stroke at 1 week after injury by enhancing the survival of ischemia-induced endogenous NPCs in SVZ. METHODS: Adult rats were subjected to a 90-minutes middle cerebral artery occlusion. A p53 inhibitor pifithrin-alpha (PFT-alpha) was administered to stroke rats from days 6 to 9 after middle cerebral artery occlusion. Locomotor behavior was measured using an activity chamber. Proliferation, survival, migration, and differentiation of endogenous NPCs were examined using quantitative reverse transcription polymerase chain reaction, terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling, and immunohistochemistry. RESULTS: PFT-alpha enhanced functional recovery as assessed by a significant increase in multiple behavioral measurements. Delayed PFT-alpha treatment had no effect on the cell death processes in the lesioned cortical region. However, it enhanced the survival of SVZ progenitor cells, and promoted their proliferation and migration. PFT-alpha inhibited the expression of a p53-dependent proapoptotic gene, termed PUMA (p53-upregulated modulator of apoptosis), within the SVZ of stroke animals. The enhancement of survival/proliferation of NPCs was further found in SVZ neurospheres in tissue culture. PFT-alpha dose-dependently increased the number and size of new neurosphere formation. INTERPRETATION: Delayed treatment with a p53 inhibitor PFT-alpha is able to modify stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. PMID- 19475674 TI - Validity, reliability, and responsiveness of the EQ-5D in inflammatory bowel disease in Germany. AB - BACKGROUND: The EuroQol (EQ)-5D questionnaire is a generic instrument measuring health-related quality of life. Its validity, reliability, and responsiveness were assessed in a large sample of Crohn's disease (CD) and ulcerative colitis (UC) patients. METHODS: The EQ-5D was completed initially (270 CD and 232 UC subjects) and after 4 weeks (447 subjects) with a transition question rating health change. Responsiveness of EQ visual analog scale (EQ-VAS) and the United Kingdom (UK-index) and German EQ-5D index (EQ-index) scores to reported changes in health was evaluated by standardized response means (SRM) and meaningful differences (MDs). RESULTS: EQ-VAS and EQ-index scores correlated well with disease activity indices and differed significantly between active disease and remission groups. All scores were reliable in test-retest (ICC: EQ-VAS: 0.89; UK index: 0.76; German EQ-index: 0.72). According to SRM, EQ-VAS was more responsive for deterioration in health than for improvement in health and was more responsive than index scores. Index scores were most responsive for deterioration in health in subjects in remission and for improved health in subjects with active disease. MDs for improved health (EQ-VAS: 10.9; UK EQ-index: 0.076; German EQ-index: 0.050) and deteriorated health (EQ-VAS: -14.4; UK EQ-index: -0.109; German EQ-index: -0.067) were significant, but MD of EQ-VAS also differed significantly according to disease activity. CONCLUSIONS: The EQ-5D generates valid, reliable, and responsive preference-based evaluations of health in CD and UC. EQ-VAS scores were more responsive than EQ-5D index scores. Thus, small health differences that are important from the patient's perspective may not be reflected in the EQ-index. PMID- 19475675 TI - A maternal high-fat diet during pregnancy in rats results in a greater risk of carcinogen-induced mammary tumors in the female offspring than exposure to a high fat diet in postnatal life. AB - The association between a high-fat diet and breast cancer risk is controversial. We hypothesized that the exposure of rats to a high-fat diet in utero via the maternal diet would result in a greater risk of carcinogen-induced mammary tumors than high-fat diet exposure in postnatal life. Rats were exposed to a high-fat diet with 40% of the energy source as safflower oil in utero (In utero group), at postnatal days 30-50 (Puberty group), postnatal days 150-170 (Adult group), postnatal days 1-230 (Postnatal group) or for their whole life from in utero (Whole group). Chow diet-fed rats were used as the Nonexposure group. Mammary tumor incidence was significantly higher in the In utero (60%), Postnatal (61%) and Whole (91%) groups than in the Nonexposure group (32%), but there was no significant difference between the Puberty (44%), Adult (44%) and Nonexposure groups. Arachidonic acid levels were 10 times higher in mammary tumor tissue than in the normal mammary gland across all groups and were positively correlated with tumor weight. We conclude that the timing, but not the duration, of high-fat diet exposure makes rats more susceptible to carcinogen-induced mammary tumors and that exposure in utero to a maternal high-fat diet during pregnancy is more important in increasing the risk of mammary tumors in the female offspring than exposure of the offspring to the same high-fat diet later in life. PMID- 19475673 TI - Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. AB - OBJECTIVE: Recent studies have identified a major locus for risk for coronary artery disease and myocardial infarction on chromosome 9p21.3. Stroke, in particular, ischemic stroke caused by atherosclerotic disease, shares common mechanisms with myocardial infarction. We investigated whether the 9p21 region contributes to ischemic stroke risk. METHODS: In an initial screen, 15 single nucleotide polymorphisms (SNPs) covering the critical genetic interval on 9p21 were genotyped in samples from Southern Germany (1,090 cases, 1,244 control subjects) and the United Kingdom (758 cases, 872 control subjects, 3 SNPs). SNPs significantly associated with ischemic stroke or individual stroke subtypes in either of the screening samples were subsequently genotyped in 2,528 additional cases and 2,189 additional control subjects from Europe and North America. RESULTS: Genotyping of the screening samples demonstrated associations between seven SNPs and atherosclerotic stroke (all p < 0.05). Analysis of the full sample confirmed associations between six SNPs and atherosclerotic stroke in multivariate analyses controlling for demographic variables, coronary artery disease, myocardial infarction, and vascular risk factors (all p < 0.05). The odds ratios for the lead SNP (rs1537378-C) were similar in the various subsamples with a pooled odds ratio of 1.21 (95% confidence interval, 1.07-1.37) under both fixed- and random-effects models (p = 0.002). The point estimate for the population attributable risk is 20.1% for atherosclerotic stroke. INTERPRETATION: The chromosome 9p21.3 region represents a major risk locus for atherosclerotic stroke. The effect of this locus on stroke appears to be independent of its relation to coronary artery disease and other stroke risk factors. Our findings support a broad role of the 9p21 region in arterial disease. PMID- 19475676 TI - Specific immuno capturing of the staphylococcal superantigen toxic-shock syndrome toxin-1 in plasma. AB - Toxic-shock syndrome is primarily caused by the Toxic-shock syndrome toxin 1 (TSST-1), which is secreted by the Gram-positive bacterium Staphylococcus aureus. The toxin belongs to a family of superantigens (SAgs) which exhibit several shared biological properties, including the induction of massive cytokine release and V(beta)-specific T-cell proliferation. In this study we explored the possibility to use monoclonal Variable domains of Llama Heavy-chain antibodies (VHH) in the immuno capturing of TSST-1 from plasma. Data is presented that the selected VHHs are highly specific for TSST-1 and can be efficiently produced in large amounts in yeast. In view of affinity chromatography, the VHHs are easily coupled to beads, and are able to deplete TSST-1 from plasma at very low, for example, pathologically relevant, concentrations. When spiked with 4 ng/mL TSST-1 more than 96% of TSST-1 was depleted from pig plasma. These data pave the way to further explore application of high-affinity columns in the specific immuno depletion of SAgs in experimental sepsis models and in sepsis in humans. PMID- 19475679 TI - The gut-liver axis in nonalcoholic fatty liver disease: Another pathway to insulin resistance? PMID- 19475680 TI - Impact factor: misused and overhyped? PMID- 19475677 TI - Microvascular lesions in the brain and retina: The age, gene/environment susceptibility-Reykjavik study. AB - OBJECTIVE: To investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly. METHODS: The study included 4,176 men and women (mean age, 76 years) who participated in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. Digital retinal images of both dilated eyes were taken and evaluated for the presence of retinal focal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) and retinopathy lesions (retinal blot hemorrhages and microaneurysms). Brain magnetic resonance imaging scans were acquired and evaluated for the presence and distribution of cerebral infarcts and WMHs. Logistic and multinomial logistic models were constructed to estimate the association of retinal microvascular signs to brain lesions. RESULTS: Controlling for demographic and major cardiovascular risk factors, we found that retinal focal arteriolar signs, but not retinopathy lesions, were significantly associated with an increasing load of subcortical and periventricular WMHs. The strongest association was found between retinal arteriolar signs and a heavier WMH load, specifically in the subcortical frontal lobe, and periventricular frontal and parietal caps. There was a tendency toward bilateral retinal focal arteriolar narrowing being more strongly associated with the heavier load of subcortical WMHs. Arteriovenous nicking was significantly associated with subcortical infarcts. INTERPRETATION: In older adults, retinal focal arteriolar signs, but not retinopathy lesions, are correlated with the load of diffuse WMHs, particularly those located in the subcortical frontal lobe, and the periventricular frontal and parietal caps of the brain. PMID- 19475683 TI - Activation of the cholehepatic shunt as a potential therapy for primary sclerosing cholangitis. PMID- 19475684 TI - Liver stiffness and hepatocellular carcinoma: liaisons dangereuses? PMID- 19475685 TI - Phenotypic differences between two Gnmt-/- mouse models for hepatocellular carcinoma. PMID- 19475687 TI - Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2-/- mice. AB - 24-norursodeoxycholic acid (norUDCA), a side chain-modified ursodeoxycholic acid derivative, has dramatic therapeutic effects in experimental cholestasis and may be a promising agent for the treatment of cholestatic liver diseases. We aimed to better understand the physiologic and therapeutic properties of norUDCA and to test if they are related to its side chain length and/or relative resistance to amidation. For this purpose, Mdr2(-/-) mice, a model for sclerosing cholangitis, received either a standard diet or a norUDCA-, tauro norursodeoxycholic acid (tauro- norUDCA)-, or di norursodeoxycholic acid (di norUDCA)-enriched diet. Bile composition, serum biochemistry, liver histology, fibrosis, and expression of key detoxification and transport systems were investigated. Direct choleretic effects were addressed in isolated bile duct units. The role of Cftr for norUDCA-induced choleresis was explored in Cftr(-/-) mice. norUDCA had pharmacologic features that were not shared by its derivatives, including the increase in hepatic and serum bile acid levels and a strong stimulation of biliary HCO(3)(-)-output. norUDCA directly stimulated fluid secretion in isolated bile duct units in a HCO(3)(-)-dependent fashion to a higher extent than the other bile acids. Notably, the norUDCA significantly stimulated HCO(3)(-)-output also in Cftr(-/-) mice. In Mdr2(-/-) mice, cholangitis and fibrosis strongly improved with norUDCA, remained unchanged with tauro- norUDCA, and worsened with di norUDCA. Expression of Mrp4, Cyp2b10, and Sult2a1 was increased by norUDCA and di norUDCA, but was unaffected by tauro- norUDCA. CONCLUSION: The relative resistance of norUDCA to amidation may explain its unique physiologic and pharmacologic properties. These include the ability to undergo cholehepatic shunting and to directly stimulate cholangiocyte secretion, both resulting in a HCO(3)(-)-rich hypercholeresis that protects the liver from cholestatic injury. PMID- 19475688 TI - Treatment of chronic hepatitis C in hemodialysis patients. PMID- 19475689 TI - Hepatitis C virus replication in patients with occult hepatitis C virus infection. PMID- 19475690 TI - Enhanced expression of vascular endothelial growth factor-A in ground glass hepatocytes and its implication in hepatitis B virus hepatocarcinogenesis. AB - Ground glass hepatocytes (GGH) in chronic hepatitis B virus (HBV) infection harbor HBV pre-S deletion mutants in endoplasmic reticulum (ER) and exhibit complex biologic features such as ER stress, DNA damage, and growth advantage. The presence of pre-S mutants in serum has been shown to predict the development of hepatocellular carcinoma (HCC) in HBV carriers. GGHs hence represent a potentially preneoplastic lesion. Whether a specific growth factor is overexpressed and activated in GGHs remains to be clarified. In this study, growth factor(s) up-regulated by pre-S mutants was identified using a growth factor array in HuH-7 cells. Immunohistochemistry, reverse-transcriptase polymerase chain reaction, and Western blot analysis were performed to study the participation of these genes and their signal pathways in HuH-7 cells and liver tissues. We demonstrate that vascular endothelial growth factor-A (VEGF-A) was up regulated by pre-S mutants in HuH-7 cells and further confirmed in GGHs by immunostaining. The VEGF-A up-regulation by pre-S mutants could be suppressed by vomitoxin, an ER stress inhibitor. Furthermore, pre-S mutants-expressed HuH-7 cells exhibited activation of Akt/mTOR (mammalian target of rapamycin) signaling and increased growth advantage, which could be inhibited by VEGF-A neutralization. Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling, comparable to the levels of paired HCC tissues, were also detected in HBV-related nontumorous livers. CONCLUSION: The enhanced expression of VEGF-A in GGHs provides potential mechanism to explain the progression from preneoplastic GGHs to HCC in chronic HBV infection. PMID- 19475691 TI - Overexpression of insulin receptor substrate-1 and hepatitis Bx genes causes premalignant alterations in the liver. AB - Activation of the insulin (IN)/insulin receptor substrate-1 (IRS-1)/mitogen associated protein kinase (MAPK) and the Wnt/beta-catenin signaling cascades occurs frequently in hepatocellular carcinoma (HCC) associated with persistent viral infection. The aims of this study were to provide a chronic proliferative stimulus through IRS-1 in the context of hepatitis Bx (HBx) protein expression in transgenic mice and determine if constitutive expression of these genes is sufficient to cause hepatocyte dysplasia and cellular transformation. We generated transgenic mice in which the HBx (ATX), IRS-1, or both (ATX+/IRS-1) genes were expressed under a liver-specific promoter. We also assessed histology and oxidative damage as well as up-regulation of molecules related to these signal transduction cascades in the liver by quantitative reverse-transcriptase polymerase chain reaction. Whereas mice with a single transgene (ATX or IRS-1) did not develop tumors, ATX+/IRS-1+ double transgenic livers had increased frequency of hepatocellular dysplasia and developed HCC. All three transgenic lines had significantly increased insulin growth factor 1 (IGF-1), Wnt 1 and Wnt 3 mRNA levels, and evidence of DNA damage and oxidative stress. The ATX+/IRS+ double transgenic mice were distinguished by having the highest level of activation of Wnt 3 and Frizzled 7 and selectively increased expression of IGF II, proliferating cell nuclear antigen, and aspartyl-(asparaginyl)-beta hydroxylase, a gene associated with increased cell migration. CONCLUSION: These results suggest that continued expression of the ATX or IRS-1 transgenes can contribute to hepatocyte transformation but are not sufficient to trigger neoplastic changes in the liver. However, dual expression that activates both the IN/IRS-1/MAPK and Wnt/beta-catenin cascades is sufficient to cause dysplasia and HCC in a previously normal liver. PMID- 19475692 TI - Nonstructural 3/4A protease of hepatitis C virus activates epithelial growth factor-induced signal transduction by cleavage of the T-cell protein tyrosine phosphatase. AB - The hepatitis C virus (HCV) is a worldwide major cause of chronic liver disease with a high tendency to establish a persistent infection. To permit persistent replication of viral genomes through the cellular translation machinery without affecting host cell viability, viruses must have developed mechanisms to control cellular cascades required for sufficient viral replication, on the one hand, and to adapt viral replication to the cellular requirements on the other hand. The present study aimed to further elucidate mechanisms by which HCV targets growth factor signaling of the host cell and their implications for viral replication. The study describes a novel mechanism by which HCV influences the activation of the epithelial growth factor receptor/Akt pathway through a nonstructural (NS)3/4A-dependent down-regulation of the ubiquitously expressed tyrosine phosphatase T cell protein tyrosine phosphatase (TC-PTP). NS3/4A is demonstrated to cleave TC-PTP protease-dependently in vitro at two cleavage sites. The in vivo relevance of this finding is supported by the fact that down-regulation of TC-PTP protein expression could also be demonstrated in HCV-infected individuals and in transgenic mice with intrahepatic expression of NS3/4A. CONCLUSION: This down regulation of TC-PTP results in an enhancement of epithelial growth factor (EGF) induced signal transduction and increases basal activity of Akt, which is demonstrated to be essential for the maintenance of sufficient viral replication. Hence, therapeutic targeting of NS3/4A may not only disturb viral replication by blocking the processing of the viral polyprotein but also exerts unforeseen indirect antiviral effects, further diminishing viral replication. PMID- 19475694 TI - Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. AB - Several circulating cytokines are increased with obesity and may combine with the influence of visceral fat to generate insulin resistance, inflammation, and fibrosis in nonalcoholic fatty liver disease (NAFLD). Little information exists in NAFLD about three recently recognized tissue-derived cytokines that are all lipid-binding and involved in inflammation, namely adipocyte fatty acid-binding protein (AFABP), lipocalin-2, and retinol-binding protein 4 (RBP4). We examined the association of these three peptides with hepatic steatosis, inflammation, and fibrosis plus indices of adiposity, insulin resistance, and dyslipidaemia in 100 subjects with NAFLD and 129 matched controls. Levels of AFABP and lipocalin-2, but not RBP4, were significantly elevated in NAFLD versus control (AFABP, 33.5 +/ 14.4 versus 23.1 +/- 12.1 ng/mL [P < 0.001]; lipocalin-2, 63.2 +/- 26 versus 48.6 +/- 20 ng/mL [P < 0.001]) and correlated with indices of adiposity. AFABP correlated with indices of subcutaneous rather than visceral fat. AFABP alone distinguished steatohepatitis from simple steatosis (P= 0.02). Elevated AFABP independently predicted increasing inflammation and fibrosis, even when insulin resistance and visceral fat were considered; this applied to lobular inflammation and ballooning (odds ratio 1.4, confidence interval 1.0-1.8) and fibrosis stage (odds ratio 1.3, confidence interval 1.0-1.7) (P < or = 0.05 for all). None of the cytokines correlated with steatosis grade. AFABP levels correlated with insulin resistance (homeostasis model assessment of insulin resistance) in controls and NAFLD, whereas lipocalin-2 and RBP4 only correlated positively with insulin resistance in controls. CONCLUSION: Circulating AFABP, produced by adipocytes and macrophages, and lipocalin-2, produced by multiple tissues, are elevated and may contribute to the metabolic syndrome in NAFLD. AFABP levels, which correlate with subcutaneous, but not visceral fat, independently predict inflammation and fibrosis in NAFLD and may have a direct pathogenic link to disease progression. PMID- 19475695 TI - Orlistat for overweight subjects with nonalcoholic steatohepatitis. PMID- 19475693 TI - Phenotypic characterization of idiosyncratic drug-induced liver injury: the influence of age and sex. AB - Increased age and female sex are suggested risk factors for drug-induced hepatotoxicity (DILI). We studied the influence of these variables on the propensity to develop DILI, as well as its clinical expression and outcome. All cases of DILI submitted to the Spanish Registry between April 1994 and August 2007 were analyzed. Six hundred three DILI cases (310 men; mean age, 54 years) showed a similar sex distribution, reaching two peaks in the 40- to 49-year-old and 60- to 69-year-old age groups. No cases were recorded in the 20- to 29-year old group. Patients aged > or =60 years accounted for 46% of the cases, with a male predominance (158 males, 118 females; P= 0.009), as opposed to younger patients. Older age was independently associated with cholestatic type of injury (odds ratio for an age interval for 1 year: 1.024 [95% confidence interval: 1.010 1.038]; male/female ratio, 1:2; P = 0.001) and younger age with hepatocellular damage (odds ratio: 0.983 [95% confidence interval: 0.972-0.994]; female/male ratio, 1:2; P = 0.002). In the mixed group, no age effect was evident. Outcome with fulminant liver failure/liver transplantation was more frequently encountered in women (P < 0.01). conclusion: Neither older age nor female sex are predisposing factors to overall DILI. However, older age is a determinant for cholestatic damage with a male predominance, whereas younger age is associated with cytolytic damage and a female overrepresentation. Women distinctly exhibit the worst outcome. Knowledge of these phenotypic associations could guide differential diagnosis and attribution of causality in DILI. PMID- 19475696 TI - Management of adult patients with ascites due to cirrhosis: an update. PMID- 19475697 TI - Meta-analysis on drugs in people with eating disorders. AB - OBJECTIVE: The aim of this study was to examine whether drug use (DU) is higher in people with eating disorders (EDs) compared to a healthy control group and to perform a meta-analysis on the literature related to DU in people with EDs. METHOD: We searched electronic databases (Medline, PsycINFO, Web of Science and CINAHL) and reviewed studies published from 1994 to August, 2007, in English, German or Spanish. A total of 16 papers fulfilled the inclusion criteria and were included. RESULTS: The general meta-analysis revealed a negligible albeit significant effect size (0.119, p < .05). Risk was found to be higher in bulimia nervosa (BN, delta = 0.462, p = < .001), smaller in binge eating disorder (delta = 0.14, p < .05) and non-significant in anorexia nervosa (AN, delta = -.167, p = .070). CONCLUSIONS: The differential risk observed in patients with BN might be related to differences in temperament or might be the result of reward sensitization. PMID- 19475698 TI - Impaired decentration in personality disorder: a series of single cases analysed with the Metacognition Assessment Scale. AB - BACKGROUND: There is growing support for the idea that an impaired understanding of others' mental states is an underlying feature of personality disorder (PD). Only recently has there begun to be evidence of impairments to subjects' ability to infer and reason about others' intentions and emotions, and detach from their own perspective when doing so. METHOD: We analysed the transcripts from the first 16 psychotherapy sessions of 14 PD patients. Scales for understanding others' minds from the Metacognition Assessment Scale were used. RESULTS: Patients were generally able to describe others' mental states, although, at times, they had problems. There was, on the other hand, an inability to decentre while reasoning about others, and this was common to all the patients. CONCLUSIONS: PDs indeed feature a poor decentration, which is not easily identified with the usual lab tasks. Implications for further research and treatment are discussed. KEY PRACTITIONER MESSAGE: *Patients with personality disorders have substantial difficulties in adopting others' point of view and standing back from their own, and grasping that they are not the center of other peoples' thoughts. PMID- 19475700 TI - A metacognitive model of problem drinking. AB - Previous research has demonstrated significant relationships between metacognition and problem drinking. In this study, we aimed to investigate further these relationships by testing the fit of a metacognitive model of problem drinking in a sample of 174 problem drinkers from a university student population. In the model presented, it is proposed that positive metacognitive beliefs about alcohol use and negative affect lead to alcohol use as a means of affect regulation. Positive metacognitive beliefs about alcohol use are also associated with a reduction in metacognitive monitoring which further contributes to alcohol use. Once alcohol use is initiated it brings a disruption in metacognitive monitoring leading to a continuation in drinking. Following a drinking episode, alcohol use is appraised as both uncontrollable and dangerous, which in turn strengthens negative metacognitive beliefs about alcohol use. These beliefs are associated with an escalation of negative affect, which acts as a trigger for further drinking. The specified relationships among these variables were examined by testing the fit of a path model. Results of this analysis indicated a good model fit consistent with predictions. The conceptual and clinical implications of these data are discussed. KEY PRACTITIONER MESSAGE: *A cognitive-attentional model that may aid assessment, conceptualization and treatment for moderate or at risk problem drinkers. PMID- 19475699 TI - Quality of life in depression: an important outcome measure in an outpatient cognitive-behavioural therapy group programme? AB - Studies have shown that psychiatric patients have significantly impaired quality of life (QOL) in comparison to community samples who are not suffering a mental illness. Despite an increase in research in the mental health field, there still remains little consensus as to the merit of using such questionnaires within a mental health population. There is a concern that QOL is redundant with affective state and symptomatology. We investigated the usefulness of the Quality of Life Enjoyment and Satisfaction Questionnaire-short form (QLESQ-SF) in a depressed outpatient sample receiving time-limited, standardized group cognitive behavioural therapy. QLESQ-SF ratings were examined at admission and 10-week endpoint in an intention-to-treat (N = 212) and completers (N = 164) sample. QLESQ-SF ratings and symptom ratings (Beck Depression Inventory-II; Beck Anxiety Inventory) improved significantly over time. Hierarchical regression analyses revealed that, although affective state and change in symptomatology were significantly correlated with QOL and change in QOL, a large proportion of variance was unexplained. These results are inconsistent with the theory of measurement redundancy. QOL appears to be a useful measure that provides additional treatment outcome information distinct from affective state and symptomatology. PMID- 19475701 TI - Continuous infusion idarubicin and intravenous busulphan as conditioning regimen to autologous stem cell transplantation for patients with acute myeloid leukaemia. AB - The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous (iv) busulfan (Bu) and continuous infusion Idarubicin (IDA) as a conditioning regimen to autologous haematopoietic stem cell transplantation (ASCT) in patients with acute myeloid leukaemia (AML). The protocol included IDA at 20 mg/sqm daily as 3 days continuous infusion (from day -13 to -11) and intravenous BU at 3.2 mg/kg daily from day -5 to -2. Patients aged over 60 years received a reduced schedule (2 days IDA and 3 days BU at the same dose). Twenty five patients with a median age of 51 years (28-72) were enrolled. All patients received peripheral blood stem cells (PBSC). The median interval between diagnosis and ASCT was 4 months. The median number of CD34+ cells infused was 5.9 x 10E6/kg. The median number of days to PMN >500/cmm and platelets >20000/cmm was 10 and 13, respectively. In order to perform a comparison in terms of haematological and non haematological toxicity, a group of 30 patients, who were previously autografted after conditioning with IDA and oral Bu was considered. Selection of factors for a matched pair analysis included median age, percentage of subjects aged over 60 years, median CD34+ cell received, cytogenetic and molecular findings and per cent of secondary AML. As compared to previous series, the occurrence of severe mucositis was dramatically reduced (80% vs. 12%, p < 0.0001). In addition, need and duration of total parenteral nutrition (TPN), iv antibiotic therapy and hospitalization were also significantly reduced. We conclude that replacement of oral with intravenous BU results in a more favourable toxicity profile. A longer follow-up is required to assess a potential advantage in terms of disease free survival (DFS). PMID- 19475702 TI - Insights into lid movements of Burkholderia cepacia lipase inferred from molecular dynamics simulations. AB - The interfacial activation of many lipases at water/lipid interface is mediated by large conformational changes of a so-called lid subdomain that covers up the enzyme active site. Here we investigated using molecular dynamic simulations in different explicit solvent environments (water, octane and water/octane interface) the molecular mechanism by which the lid motion of Burkholderia cepacia lipase might operate. Although B. cepacia lipase has so far only been crystallized in open conformation, this study reveals for the first time the major conformational rearrangements that the enzyme undergoes under the influence of the solvent, which either exposes or shields the active site from the substrate. In aqueous media, the lid switches from an open to a closed conformation while the reverse motion occurs in organic environment. In particular, the role of a subdomain facing the lid on B. cepacia lipase conformational rearrangements was investigated using position-restrained MD simulations. Our conclusions indicate that the sole mobility of alpha9 helix side chains of B. cepacia lipase is required for the full completion of the lid conformational change which is essentially driven by alpha5 helix movement. The role of selected alpha5 hydrophobic residues on the lid movement was further examined. In silico mutations of two residues, V138 and F142, were shown to drastically modify the conformational behavior of B. cepacia lipase. Overall, our results provide valuable insight into the role played by the surrounding environment on the lid conformational rearrangement and the activation of B. cepacia lipase. PMID- 19475703 TI - Crystal structure of NusG N-terminal (NGN) domain from Methanocaldococcus jannaschii and its interaction with rpoE''. AB - Transcription in archaea employs a eukaryotic-type transcription apparatus but uses bacterial-type transcription factors. NusG is one of the few archaeal transcription factors whose orthologs are essential in both bacteria and eukaryotes. Archaeal NusG is composed of only an NusG N-terminal (NGN) domain and a KOW domain, which is similar to bacterial NusG but not to the eukaryotic ortholog, Spt5. However, archaeal NusG was confirmed recently to form a complex with rpoE'' that was similar to the Spt5-Spt4 complex. Thus, archaeal NusG presents hybrid features of Spt5 and bacterial NusG. Here we report the crystal structure of NGN from the archaea Methanocaldococcus jannaschii (MjNGN). MjNGN folds to an alpha-beta-alpha sandwich without the appendant domain of bacterial NGNs, and forms a unique homodimer in crystal and solution. MjNGN alone was found to be sufficient for rpoE'' binding and an MjNGN-rpoE'' model has been constructed by rigid docking. PMID- 19475704 TI - Predicting structurally conserved contacts for homologous proteins using sequence conservation filters. AB - The prediction of intramolecular contacts has a useful application in predicting the three-dimensional structures of proteins. The accuracy of the template-based contact prediction methods depends on the quality of the template structures. To reduce the false positive predictions associated with using the entire set of template-derived contacts, we develop selection filters that use sequence conservation information to predict subsets of contacts more likely to be structurally conserved between the template and the target. The method is developed specifically for protein families with few available templates such as the G protein-coupled receptor (GPCR) family. It is validated on a test set of 342 template-target pairs from three protein families, and applied to one template-target pair from the GPCR family. We find that the filter selection method increases the accuracy of contact prediction with sufficient coverage for structure prediction. PMID- 19475705 TI - Xanthomonas campestris PqqD in the pyrroloquinoline quinone biosynthesis operon adopts a novel saddle-like fold that possibly serves as a PQQ carrier. PMID- 19475707 TI - Weight loss reduces urinary incontinence in heavy women. PMID- 19475706 TI - Effects of three different doses of a fruit extract of Terminalia chebula on metabolic components of metabolic syndrome, in a rat model. AB - There is documented evidence of the use of Terminalia chebula for various ailments in the Ayurvedic literature. The extract has been shown to possess glucose lowering activity and to improve insulin sensitivity in animal models of type 2 diabetes mellitus. The present study was carried out to study the dose response relationship of this extract in a rat model of metabolic syndrome. Six groups of rats were fed a high fructose diet (HFD) for a period of 20 days to induce metabolic syndrome. Three doses of fruit extract of T. chebula 50, 100 and 200 mg/kg were administered orally and pioglitazone 2.7 mg/kg was used as a positive control. Blood samples were collected at days 0, 20 and 40 from the tail vein. Systolic blood pressure (SBP) was measured using the tail cuff method and an oral glucose tolerance test (OGTT) was done on the day of blood collection. Administration of HFD for 20 days significantly increased fasting blood glucose (FBG), SBP and the area under the curve of OGTT. On day 40 the FBG in the 50, 100 and 200 mg/kg group was 97.33 +/- 5.82 (NS), 86.83 +/- 5.08 (p = 0.038) and 85.67 +/- 6.74 (p = 0.15), respectively. These results show that the fruit extract of T. chebula exerts a significant and dose-dependent glucose lowering effect in the rat model of metabolic syndrome. PMID- 19475708 TI - By the way, doctor. I'm 78. I had breast cancer nine years ago and have been taking Arimidex for six years. I have pain and some bleeding after intercourse, despite using Astroglide. My gynecologist prescribed vaginal estrogen cream. Is that safe for me? PMID- 19475709 TI - Escape from the Ponto-Caspian: evolution and biogeography of an endemic goby species flock (Benthophilinae: Gobiidae: Teleostei). AB - Endemic Ponto-Caspian gobies include a flock of 24 "neogobiin" species (containing the nominal genera and subgenera Apollonia, Babka, Neogobius, Mesogobius, Ponticola, and Proterorhinus; Teleostei: Gobiidae), of which a large proportion (5 species; 21%) recently escaped to invade other freshwater Eurasian systems and the North American Great Lakes. We provide its first comprehensive phylogenetic and biogeographic analysis based on 4709 bp sequences from two mitochondrial and two nuclear genes with maximum parsimony, likelihood, and Bayesian approaches. We additionally compare its relationships with the tadpole gobies (Benthophilus and Caspiosoma), which comprise a related endemic Ponto Caspian gobiid group; along with a variety of postulated relatives and outgroups. Results of all phylogenetic approaches are highly congruent and provide very strong support for recognizing the subfamily Benthophilinae; which encompasses both the "neogobiins" and tadpole gobies, and genetically diverges from other Gobiidae subfamilies-including (non-monophyletic) Gobiinae and Gobinellinae. Benthophilinae contains three tribes: Neogobiini (Neogobius, which is synonymized here with Apollonia; containing the type species N. fluviatilis, along with N. melanostomus and N. caspius), Ponticolini (containing the genera Mesogobius, Proterorhinus, Babka, and Ponticola-elevating the latter two from subgenera and removing them from the formerly paraphyletic Neogobius), and Benthophilini (tadpole gobies). Within Ponticolini, Proterorhinus and Mesogobius comprise the sister clade of the Ponticola and Babka clade. Further work is needed to clarify the interrelationships of the tadpole gobies. Invasiveness is widespread in freshwater and euryhaline taxa of Neogobius, Proterorhinus, Babka, and Ponticola; but not in marine species, Mesogobius, or tadpole gobies. PMID- 19475710 TI - The first comprehensive molecular phylogeny of Bryozoa (Ectoprocta) based on combined analyses of nuclear and mitochondrial genes. AB - Bryozoa is one of the most puzzling phyla in the animal kingdom and little is known about their evolutionary history. Its phylogenetic position among the Metazoa remains unsettled, as well as its intra-phylum relationships. Here, we present the first comprehensive molecular phylogeny of Bryozoa based on the mitochondrial gene COI and two nuclear genes 18S rDNA and 28S rDNA including 32 species from 23 families. We show that the monophyletic status is supported for the phylum as well as for previously defined bryozoan classes. The 28S rDNA supports a close relationship of Phylactolaemata and Stenolaemata, while partial COI and 18S rDNA show the freshwater Phylactolaemata as basal bryozoans. The Gymnolaemata have generally been divided into soft-bodied forms (Ctenostomata) and hard-bodied species (Cheilostomata). In our analyses all three genes conflict with this assumption and show hard body forms having evolved within Gymnolaemata several times. PMID- 19475711 TI - Phylogenetic relationships of Gymnothorax bacalladoi Bohlke and Brito (1987) a poorly known moray of the Macaronesian islands. PMID- 19475712 TI - New insights into the phylogeny of glass sponges (Porifera, Hexactinellida): monophyly of Lyssacinosida and Euplectellinae, and the phylogenetic position of Euretidae. PMID- 19475713 TI - MtZoa: a general mitochondrial amino acid substitutions model for animal evolutionary studies. PMID- 19475714 TI - [In memoriam. Remembering Filippo Soricelli]. PMID- 19475715 TI - Divergence to apoptosis from ROS induced cell cycle arrest: effect of cadmium. AB - Recently, the role of cadmium (Cd) in immunosupression has gained importance. Nevertheless, the signaling pathways underlying cadmium-induced immune cell death remains largely unclear. In accordance to our previous in vivo report, and to evaluate the further details of the mechanism, we have investigated the effects of cadmium (CdCl(2), H(2)O) on cell cycle regulation and apoptosis in splenocytes in vitro. Our results have revealed that reactive oxygen species (ROS) and p21 are involved in cell cycle arrest in a p53 independent manner but late hour apoptotic response was accompanied by the p53 up-regulation, loss of mitochondrial transmembrane potential (MTP), down-regulation of Bcl-xl, activation of caspase-3 and release of cytochrome c (Cyt c). However, pifithrin alfa (PFT-alpha), an inhibitor of p53, fails to rescue the cells from the cadmium induced cell cycle arrest but prevents Bcl-xl down-regulation and loss of Deltapsi(m), which indicates that there is an involvement of p53 in apoptosis. In contrast, treatment with N-acetyl cysteine (NAC) can prevent cell cycle arrest and p21 up-regulation at early hours. Although it is clear that, NAC has no effect on apoptosis, p53 expression and MPT changes at late stage events. Taken together, we have demonstrated that cadmium promotes ROS generation, which potently initiates the cell cycle arrest at early hours and finally induces p53 dependent apoptosis at later part of the event. PMID- 19475717 TI - Molecular mechanisms underlying large genomic deletions in ornithine transcarbamylase (OTC) gene. AB - Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle error causing hyperammonemia and orotic aciduria. Clinical diagnosis is generally confirmed by mutation detection. However, in approximately 20% of the patients, no mutation is found by conventional mutation-searching strategies, which fail to detect deletions spanning at least a whole exon, large rearrangements, or mutations at non-coding regions. To detect large deletions or duplications, we have applied the multiplex ligation-dependent probe amplification (MLPA) methodology to three OTCD patients (two females and one male). MLPA revealed copy number alterations of OTC exons in all of them. The two females were found to be heterozygous for deletions of either exon 2 or exons 6-9, and the male was confirmed to lack all OTC exons. Females' characterization of the deletion breakpoints by long polymerase chain reaction and sequencing revealed the mutations c.78-3544_217-129del5921 and c.541-600_1005 + 1880del10862 corresponding to exon 2 and exon 6-9 deletions, respectively. Examination of the deletion-flanking regions suggests that exon 2 deletion probably resulted from replication slippage facilitated by a secondary structure formed by two inverted Alu repeats, whereas an Alu-Alu homologous recombination was probably responsible for the exon 6-9 deletion. This work contributes to the identification of novel disease-causing mutations in OTCD and increases the knowledge on possible mutational mechanisms generating deletions in OTC. PMID- 19475718 TI - Recurrence risk due to germ line mosaicism: Duchenne and Becker muscular dystrophy. AB - The presence of multiple affected offspring from apparently non-carrier parents is caused by germ line mosaicism. Although germ line mosaicism has been reported for many diseases, figures for recurrence risks are known for only a few of them. In X-linked Duchenne and Becker muscular dystrophies (DMD/BMD), the recurrence risk for non-carrier females due to germ line mosaicism has been estimated to be between 14% and 20% (95% confidence interval 3-30) if the risk haplotype is transmitted. In this study, we have analyzed 318 DMD/BMD cases in which the detected mutation was de novo with the aim of obtaining a better estimate of the 'true' number of germ line mosaics and a more precise recurrence risk. This knowledge is essential for genetic counseling. Our data indicate a recurrence risk of 8.6% (4.8-12.2) if the risk haplotype is transmitted, but there is a remarkable difference between proximal (15.6%) (4.1-27.0) and distal (6.4%) (2.1 10.6) deletions. Overall, most mutations originated in the female. Deletions occur more often on the X chromosome of the maternal grandmother, whereas point mutations occur on the X chromosome of the maternal grandfather. In unhaplotyped de novo DMD/BMD families, the risk of recurrence of the mutation is 4.3%. PMID- 19475716 TI - The spectrum of ABCC8 mutations in Norwegian patients with congenital hyperinsulinism of infancy. AB - Potassium channels in the plasma membrane of the pancreatic beta cells are critical in maintaining glucose homeostasis by responding to ATP and coupling metabolic changes to insulin secretion. These channels consist of subunits denoted the sulfonylurea receptor SUR1 and the inwardly rectifying ion channel KIR6.2, which are encoded by the genes ABCC8 and KCNJ11, respectively. Activating mutations in the subunit genes can result in monogenic diabetes, whereas inactivating mutations are the most common cause of congenital hyperinsulinism of infancy (CHI). Twenty-six Norwegian probands with CHI were analyzed for alterations in ABCC8 and KCNJ11. Fifteen probands (58%) had mutations in the ABCC8 gene. Nine patients were homozygous or compound heterozygous for the mutations, indicating diffuse pancreatic disease. In five patients, heterozygous and paternally inherited mutations were found, suggesting focal disease. One patient had a de novo mutation likely to cause a milder, dominant form of CHI. Altogether, 16 different ABCC8 mutations (including the novel alterations W231R, C267X, IVS6-3C>G, I462V, Q917X and T1531A) were identified. The mutations IVS10+1G>T, R1493W and V21D occurred in five, three and two families, respectively. KCNJ11 mutations were not found in any patients. Based on our mutation screening, we estimate the minimum birth prevalence of ABCC8-CHI in Norway to 1:70,000 during the past decade. Our results considerably extend the knowledge of the molecular genetics behind CHI in Scandinavia. PMID- 19475719 TI - Proven germline mosaicism in a father of two children with CHARGE syndrome. AB - CHARGE syndrome is an autosomal dominant malformation syndrome caused by mutations in the CHD7 gene. The majority of cases are sporadic and only few familial cases have been reported. In these families, mosaicism in one parent, as well as parent- to-child transmission of a CHD7 mutation, has been described. In some further cases, germline mosaicism has been suggested. Here, we report the first case in which germline mosaicism could be demonstrated in a father of two affected children with CHARGE syndrome. The truncating mutation c.7302dupA in exon 34 of the CHD7 gene was found in both affected children but was not detected in parental lymphocytes. However, in DNA extracted from the father's spermatozoa, the c.7302dupA mutation could be identified. Furthermore, mutation analysis of DNA isolated from 59 single spermatozoa revealed that the c.7302dupA mutation occurs in 16 spermatozoa, confirming germline mosaicism in the father of the affected children. This result has a high impact for genetic counselling of the family and for their recurrence risk in further pregnancies. PMID- 19475720 TI - Factors that affect hearing level in individuals with the mitochondrial 1555A.G mutation. AB - The mitochondrial 1555A>G mutation is one of the most common mutations responsible for hearing loss in Asians. Although the association with aminoglycoside exposure is well known, there is great variation in the severity of hearing loss. We analyzed hearing levels in 221 Japanese individuals with this mutation and attempted to identify relevant covariants including (i) age, (ii) aminoglycoside exposure, (iii) heteroplasmy ratio, and (iv) other gene mutations. At every age, average hearing levels were worse than those in normal subjects, suggesting that mitochondrial function itself may affect the severity of hearing loss. Although the hearing loss in individuals with the 1555A>G mutation progressed with age, the rate did not differ from that of the normal subjects. Those who had reported aminoglycoside exposure had moderate-to-severe hearing impairment regardless of age, confirming that such exposure is the most important environmental variable. We also confirmed the presence of heteroplasmy, which is known to modify the expression of other mitochondrial diseases, but found no evidence for a significant correlation with hearing impairment. A high prevalence of GJB2 heterozygous mutations was noted, indicating that these mutations may exhibit epistatic interaction with the 1555A>G mutation. PMID- 19475721 TI - Aberrant splicing due to a silent nucleotide change in CCM2 gene in a family with cerebral cavernous malformation. PMID- 19475722 TI - Cytogenetic microarrays in Manitoba patients with developmental delay. PMID- 19475723 TI - Pilot study to evaluate the efficacy and tolerability of levetiracetam (Keppra) in treatment of patients with trigeminal neuralgia. AB - BACKGROUND AND PURPOSE: The objective of this study was to determine whether levetiracetam (LEV) is an effective drug for treatment of trigeminal neuralgia (TN). METHODS: Ten patients with TN were enrolled in a 10-week, prospective, open label pilot study. The primary outcome measure was the visual analogue scale on daily pain diary and side effects. Serum levels of LEV were measured to assess correlation between drug levels and pain control. RESULTS: There was a significant tendency towards improvement in pain severity compared with baseline in four patients with higher doses of 4,000 mg/day. The four treatment responders had less pain compared with baseline (50-90% improvement) and three subjects continued the drug after study completion. All patients rated themselves on the global evaluation scale as much improved (n = 2), minimally improved (n = 3), no change (n = 1), minimally worse (n = 2), much worse (n = 1) and very much worse (n = 1). LEV was very well tolerated and there was no difference in side effects between the low and high doses of LEV evaluations. CONCLUSION: Given its established safety profile, a randomized, placebo-controlled, double-blind trial of LEV using enhancement enrollment design is needed to confirm these open labelled findings using a wide variety of outcome measures. PMID- 19475724 TI - Auditing associative relations across two knowledge sources. AB - OBJECTIVES: This paper proposes a novel semantic method for auditing associative relations in biomedical terminologies. We tested our methodology on two Unified Medical Language System (UMLS) knowledge sources. METHODS: We use the UMLS semantic groups as high-level representations of the domain and range of relationships in the Metathesaurus and in the Semantic Network. A mapping created between Metathesaurus relationships and Semantic Network relationships forms the basis for comparing the signatures of a given Metathesaurus relationship to the signatures of the semantic relationship to which it is mapped. The consistency of Metathesaurus relations is studied for each relationship. RESULTS: Of the 177 associative relationships in the Metathesaurus, 84 (48%) exhibit a high-degree of consistency with the corresponding Semantic Network relationships. Overall, 63% of the 1.8 M associative relations in the Metathesaurus are consistent with relations in the Semantic Network. CONCLUSION: The semantics of associative relationships in biomedical terminologies should be defined explicitly by their developers. The Semantic Network would benefit from being extended with new relationships and with new relations for some existing relationships. The UMLS editing environment could take advantage of the correspondence established between relationships in the Metathesaurus and the Semantic Network. Finally, the auditing method also yielded useful information for refining the mapping of associative relationships between the two sources. PMID- 19475726 TI - The NCI Thesaurus quality assurance life cycle. AB - The National Cancer Institute Enterprise Vocabulary Services (NCI EVS) uses a wide range of quality assurance (QA) techniques to maintain and extend NCI Thesaurus (NCIt). NCIt is a reference terminology and biomedical ontology used in a growing number of NCI and other systems that extend from translational and basic research through clinical care to public information and administrative activities. Both automated and manual QA techniques are employed throughout the editing and publication cycle, which includes inserting and editing NCIt in NCI Metathesaurus. NCI EVS conducts its own additional periodic and ongoing content QA. External reviews, and extensive evaluation by and interaction with EVS partners and other users, have also played an important part in the QA process. There have always been tensions and compromises between meeting the needs of dependent systems and providing consistent and well-structured content; external QA and feedback have been important in identifying and addressing such issues. Currently, NCI EVS is exploring new approaches to broaden external participation in the terminology development and QA process. PMID- 19475725 TI - The Neighborhood Auditing Tool: a hybrid interface for auditing the UMLS. AB - The UMLS's integration of more than 100 source vocabularies, not necessarily consistent with one another, causes some inconsistencies. The purpose of auditing the UMLS is to detect such inconsistencies and to suggest how to resolve them while observing the requirement of fully representing the content of each source in the UMLS. A software tool, called the Neighborhood Auditing Tool (NAT), that facilitates UMLS auditing is presented. The NAT supports "neighborhood-based" auditing, where, at any given time, an auditor concentrates on a single-focus concept and one of a variety of neighborhoods of its closely related concepts. Typical diagrammatic displays of concept networks have a number of shortcomings, so the NAT utilizes a hybrid diagram/text interface that features stylized neighborhood views which retain some of the best features of both the diagrammatic layouts and text windows while avoiding the shortcomings. The NAT allows an auditor to display knowledge from both the Metathesaurus (concept) level and the Semantic Network (semantic type) level. Various additional features of the NAT that support the auditing process are described. The usefulness of the NAT is demonstrated through a group of case studies. Its impact is tested with a study involving a select group of auditors. PMID- 19475727 TI - Relationship auditing of the FMA ontology. AB - The Foundational Model of Anatomy (FMA) ontology is a domain reference ontology based on a disciplined modeling approach. Due to its large size, semantic complexity and manual data entry process, errors and inconsistencies are unavoidable and might remain within the FMA structure without detection. In this paper, we present computable methods to highlight candidate concepts for various relationship assignment errors. The process starts with locating structures formed by transitive structural relationships (part_of, tributary_of, branch_of) and examine their assignments in the context of the IS-A hierarchy. The algorithms were designed to detect five major categories of possible incorrect relationship assignments: circular, mutually exclusive, redundant, inconsistent, and missed entries. A domain expert reviewed samples of these presumptive errors to confirm the findings. Seven thousand and fifty-two presumptive errors were detected, the largest proportion related to part_of relationship assignments. The results highlight the fact that errors are unavoidable in complex ontologies and that well designed algorithms can help domain experts to focus on concepts with high likelihood of errors and maximize their effort to ensure consistency and reliability. In the future similar methods might be integrated with data entry processes to offer real-time error detection. PMID- 19475728 TI - G-quadruplex compounds and cis-platin act synergistically to inhibit cancer cell growth in vitro and in vivo. AB - The ability of two structurally diverse telomeric G-quadruplex-binding compounds to synergise the action of cis-platin has been investigated in two cancer cell lines. One compound is a trisubstituted acridine compound AS1410, a close analogue of BRACO-19, and the other is a non-polycyclic compound synthesised using click chemistry and containing two triazole rings. Both compounds produce growth arrest at sub-cytotoxic concentrations in the two cell lines (MCF7 and A549), with behaviour consistent with telomere targeting mechanisms. Synergistic behaviour was observed in both cell lines with both compounds in combination with cis-platin, but only when the ratio of AS1410:cis-platin is >1. In vivo tumour xenograft studies with the A549 lung cancer model and the trisubstituted acridine compound AS1410 showed only a modest anti-tumour effect when administered alone, but produced rapid and highly significant decreases in tumour volume when administered in combination with cis-platin. PMID- 19475729 TI - Development and application of a reverse transcriptase polymerase chain reaction to detect Chinese isolates of duck hepatitis virus type 1. AB - We developed a reverse transcriptase polymerase chain reaction (RT-PCR) method for the detection of duck hepatitis virus type 1 (DHV-1) in the tissues of infected and clinically affected ducks and in chick and duck embryos. We found the assay to be effective in detecting the virus in China, where it is being used in studies on the epidemiology of the disease. We applied this simple and rapid diagnostic method to the detection of DHV isolates grown in chick and duck embryos and in tissues obtained from infected birds. The assay also proved useful for the differentiation of DVH from the duck plague virus (DPV), muscovy parvovirus (MPV), gosling parvovirus (GPV), avian influenza virus (AIV/H5N1), Pasteurella multocida (PA/5:A), Riemerella anatipestifer (RA/serotype 1), and Salmonella enteritidis (SE). The limit of the sensitivity of this method for the detection of DHV-1 RNA was 3 pg/10 microl. As compared to Dot-ELISA and virus isolation, the rate of agreement for the detection of experimentally infected livers was 100%; moreover, the RT-PCR method was also capable of detecting DHV-1 RNA from the livers that had been infected and stored at -20 degrees C for 22 years; in contrast, Dot-ELISA and virus isolation method could only detect DHV-1 from the livers that had been infected and stored at -20 degrees C for 13 and 11 years, respectively. The rate of positivity in 185 clinically suspected diseased livers subjected to detection by RT-PCR, Dot-ELISA, and virus isolation was 89.2%, 69.2%, and 55.7%, respectively. These results indicated that the RT-PCR approach is rapid, sensitive, and reliable for the detection and differentiation of DHV-1 from the other clinical samples and suspected isolates. PMID- 19475731 TI - Training of care home staff. PMID- 19475730 TI - Genetic architecture of hemoglobin F control. PMID- 19475732 TI - Bridging the communication gap. PMID- 19475733 TI - Toxoplasmosis during pregnancy and infancy. A new approach for Switzerland. PMID- 19475734 TI - [Endometrioid adenocarcinoma found in the ovary and endometrium: pathologic and therapeutic particularities]. PMID- 19475735 TI - [Giant hemangiomas of the liver: report of three cases]. PMID- 19475736 TI - [Epidermoid cyst of the spleen: three cases]. PMID- 19475737 TI - [Pregnancy in myasthenic women]. PMID- 19475738 TI - Pseudotumoral actinomycosis of the central nervous system. PMID- 19475740 TI - [Granulosa cell tumor]. PMID- 19475739 TI - [Retroperitoneal mucinous cystadenoma: a case report]. PMID- 19475741 TI - [Temporal arteritis revealed by dysphagia]. PMID- 19475742 TI - [Erosive oral lichen planus in children]. PMID- 19475743 TI - [Hereditary hemorrhagic telangiectasia in pregnancy]. PMID- 19475745 TI - Getting to know ACS staff. PMID- 19475744 TI - [Solitary fibrous tumour originating in the mesentery: diagnostic and prognostic problems (a case report)]. PMID- 19475746 TI - Surgical workforce shortage. PMID- 19475747 TI - Surgical workforce shortage. PMID- 19475748 TI - Locum tenens. PMID- 19475749 TI - Laparoscopy in third-world countries. PMID- 19475750 TI - Fatal outcome of epileptic seizure-induced takotsubo syndrome with left ventricular rupture. PMID- 19475751 TI - Excessive yawning induced by stimulation of myofascial trigger point--case report. PMID- 19475752 TI - Medical implications of excessive yawning in relation to thermoregulatory dysfunction. PMID- 19475753 TI - Adjunctive dexamethasone therapy for bacterial meningitis in adults: a meta analysis of randomized controlled trials. AB - The objective of this review was to study the effectiveness of dexamethasone for the treatment of adult patients with bacterial meningitis. Data was extracted from randomized controlled trials (RCTs) comparing dexamethasone with placebo or no treatment and pooled using meta-analysis techniques. Treatment with dexamethasone was associated with a non-significant lower mortality than placebo or no treatment [odds ratio (OR) = 0.68, 95% confidence interval (CI) 0.45-1.04]. If a RCT conducted in Malawi was excluded from the analysis, dexamethasone was associated with lower mortality than placebo or no treatment (OR = 0.58, 95% CI 0.40-0.83). Dexamethasone was associated with lower mortality in patients with definite meningitis (OR = 0.55, 95% CI 0.31-0.96), short duration of symptoms (OR = 0.61, 95% CI 0.38-1.00), Streptococcus pneumoniae meningitis (OR = 0.26, 95% CI 0.08-0.78), patients in countries with high (OR = 0.45, 95% CI 0.23-0.87) and medium Human Development Index (OR = 0.65, 95% CI 0.42-1.00). No benefit was seen in patients with longer duration of symptoms (OR = 0.80, 95% CI 0.47-1.36) or no antibiotic use (OR = 0.68, 95% CI 0.36-1.28). Dexamethasone was associated with fewer episodes of hearing impairment in high quality RCTs (OR = 0.64, 95% CI 0.43 0.94). The currently available evidence suggests that dexamethasone should be administered to all adult patients with bacterial meningitis. Large studies are needed to clarify the role of the duration of symptoms, disease severity, and antibiotic administration before the initiation of treatment with dexamethasone on modifying the outcomes. PMID- 19475754 TI - Quality of life in 1000 patients with early relapsing-remitting multiple sclerosis. AB - BACKGROUND AND PURPOSE: To examine the quality of life (QoL) in a large cohort of untreated patients with relapsing-remitting multiple sclerosis (RRMS) and to investigate the impact of intramuscular (IM) interferon beta-1a (IFNbeta-1a) treatment. METHODS: Prospective, observational, open-label, multicentre study conducted in Germany. Untreated patients with RRMS who initiated treatment with IM IFNbeta-1a were included and followed for 12 months. QoL was measured using the EQ-5D questionnaire. Clinical response was assessed by relapse rate and disability (Expanded Disability Status Scale; EDSS). RESULTS: A total of 1157 patients were included [mean age 37.6 years, median disease duration 13 months, mean relapse rate 1.7 (95%CI: 1.58-1.73), median EDSS score 2.0]. Relapse rate was reduced to 0.6 at 12 months (95%CI: 0.51-0.69, P < 0.0001). EDSS did not change significantly. At baseline, QoL was considerably lower in MS patients compared with the general German population, but was improved after treatment initiation [utilities of EQ-5D: 0.77 (95%CI: 0.75-0.78) vs. 0.75 (95%CI: 0.74 0.76) at baseline, 95%CI for difference: 0.01-0.03, P = 0.0046]. Higher disease activity and inability to work were negative predictors of QoL. 14.7% of patients were incapable of working for MS-related reasons. CONCLUSIONS: Quality of life is considerably impaired in early stages of MS. Treatment initiation with IM IFNbeta attenuates MS disease activity and improves QoL. Inability to work early during the disease is a major challenge for the social security systems. PMID- 19475755 TI - Incidence and predictors of post-stroke aphasia: the Arcadia Stroke Registry. AB - BACKGROUND AND PURPOSE: Aphasia is an important post-stroke sequela. We estimated the prevalence and main determinants of post-stroke aphasia in the prefecture of Arcadia, Greece. METHOD: Prospective population-based study of Arcadia residents diagnosed with first ever stroke. within a 2 year period. Associations of aphasia with potential predictors were analysed by logistic regression in: (i) the entire cohort and (ii) the sub-cohort of patients who were alive 28 days post-stroke. Multivariate regression models were adjusted for left hemispheric stroke localization and modified Rankin Scale 28 days post-stroke (MRS-1mo). RESULTS: Of 555 subjects, 126 (22.7%) suffered from aphasia. When only the 405 survivors were considered, 77 (19.0%) suffered from aphasia. In adjusted multivariate models of the entire cohort, factors conferring significantly higher risk for aphasia included female gender, diabetes mellitus (borderline significance) and heart disease. In adjusted multivariate models of survivors, only diabetes was associated with significantly higher risk for aphasia. CONCLUSIONS: Female gender, diabetes and heart disease were independent prospective predictors of aphasia. The study offers a quantitative estimate of the public health problem of post-stroke aphasia in Greece and suggests that the role of diabetes in post stroke aphasia may be more important than previously appreciated. PMID- 19475756 TI - Incidence and lifetime risk of motor neuron disease in the United Kingdom: a population-based study. AB - BACKGROUND AND PURPOSE: To estimate the incidence and lifetime risk of motor neuron disease (MND) in a population-based sample in the United Kingdom. METHODS: We identified new cases of MND during the period 1990-2005 in the General Practice Research Database, which includes clinical information from more than 3 million Britons enrolled with selected general practitioners. Individuals with a first medical diagnosis of MND recorded in the database were considered incident cases of the disease. The positive predictive value of the computer-based diagnosis was estimated through review of a sample of medical records from potential MND cases. RESULTS: In the period 1990-2005, 830 new cases of MND were identified. Age-standardized incidence of MND was 2.6 per 100 000 persons per year in women (95% CI: 2.3, 2.8) and 3.9 in men (95% CI: 3.6, 4.3). Incidence for both sexes peaked between 75 and 79 years. The rate of MND in men was 54% higher than in women (95% CI: 33%, 77%). The lifetime risk of MND, adjusting for competing causes of death, was 1 in 472 (2.1 per 1000) in women and 1 in 350 (2.9 per 1000) in men. No increase in MND incidence over time was apparent. CONCLUSION: In this population-based database, we found that MND incidence is higher in men than women, peaking in both sexes between 75 and 79 years. PMID- 19475757 TI - Comorbidity between CIDP and diabetes mellitus: only a matter of chance? AB - BACKGROUND AND PURPOSE: It is well known that chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetes mellitus (DM) are often associated, but it is not clear if these two disorders are patogenetically correlated. METHODS: An epidemiological study on CIDP in two Italian regions (population 4,334,225) was performed, using multiple concurrent sources of cases. The presence of DM was assessed on basis of the data reported in the clinical records of each patient. Standardized morbidity ratio (SMR) was calculated, using as reference the prevalence of DM in northern Italy. RESULTS: At the prevalence day 155 patients with CIDP resident in Piemonte and Valle d'Aosta were found. Of these, 14 were also affected by either type 1 or type 2 DM. The number of expected individuals with associated DM was 13.03, corresponding to a SMR of 1.07 [95% confidence intervals (CI), 0.58-1.80]. Patients with CIDP associated with DM had a higher level of CSF proteins and a longer delay from onset to diagnosis than patients without DM, but did not differ for age of onset, gender distribution, and type of clinical course. CONCLUSIONS: Our epidemiological findings do not support a pathogenetic correlation between DM and CIDP. PMID- 19475758 TI - In ataxia-teleangiectasia betamethasone response is inversely correlated to cerebellar atrophy and directly to antioxidative capacity. AB - BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by alterations of the A-T mutated (ATM) gene. Although A-T is a non-curable disease, we, previously, documented a clear improvement of cerebellar functions during a short-term betamethasone trial. The aim of this study was to define the underlying biochemical mechanism. METHODS: In six A-T patients receiving a short-term steroid therapy, intracellular glutathione (GSH) levels were evaluated with a colorimetric assay. The lipid peroxidation level and reactive oxygen species (ROS) production were evaluated using commercial assays. All the parameters were compared with the improvement of cerebellar functions expressed as delta (Delta) of the Scale for the Assessment and Rating of Ataxia (SARA). RESULTS: We observed an inverse correlation between Delta SARA and the severity of cerebellar atrophy and between the latter and basal GSH values. Four of the five patients with the highest Delta SARA also had the highest GSH values. Moreover, even though basal ROS values were comparable in patients and controls, in the only patient studied at different time-points of therapy, a remarkable reduction in ROS levels was documented. CONCLUSION: We suggest that antioxidative mechanisms play a role in favouring the improvement of cerebellar functions observed in A-T patients receiving a short-term betamethasone trial. PMID- 19475759 TI - EFNS guidelines on disease-specific CSF investigations. AB - We reviewed the literature for disease-specific markers in cerebrospinal fluid (CSF) and evaluated their diagnostic and prognostic relevance in neurological diseases. High tau protein in combination with low amyloid beta levels has a high sensitivity (80%) and specificity (90%) for Alzheimer's disease (AD) against normal aging and can predict conversion of mild cognitive impairment to AD. The detection of 14-3-3 has a high sensitivity (80-90%) and specificity (90%) for the diagnosis of CJD. Low or undetectable CSF hypocretin-1 (orexin-1) levels constitute a diagnostic biomarker for narcolepsy with cataplexy. Detection of beta-2-transferrin indicates CSF contamination in oto- and rhinorrhoe with a sensitivity of > 79% at a specificity of 95% similar to the beta-trace protein (sensitivity > 90%, specificity 100%). However, beta-trace protein is faster and cheaper to perform. Possible future biomarkers are: elevated levels of vascular endothelial growth factor are relatively sensitive (51-100%) and specific (73 100%) for leptomeningeal metastases from solid tumors and are associated with a poor prognosis in this condition. Elevated CSF neurofilament (Nf) levels probably reflect acute neuronal degeneration. The prognostic value of CSF Nf levels is highest in acute conditions such as subarachnoid hemorrhage, acute optic neuritis and neuromyelitis optica. PMID- 19475760 TI - Effects of vitamin K1 on fluoride-induced bone changes in growing rats: a histomorphometric and radiodensitometric study. AB - The aim of this study was to investigate the potential effects of vitamin K1 supplementation on skeletal changes related to fluoride in growing rats. Forty male Wistar rats aged 4 weeks were assigned at random into three groups: high dose fluoride (125 ppm) group; high-dose fluoride + vitamin K1 (0.2 mg/(g day)) group; and a control group. The experimental period was 12 weeks. The L3 vertebrae and the right tibiae were removed, and specimens were analysed by histologic and histomorphometric methods. Quantitative radiodensitometry was also employed to assess the differences in bone mineral density (BMD) between the groups. In the tibia, total tissue area was higher in the study groups than the control group (P < 0.05). Cortical bone area was slightly higher in the fluoride + K1 group than the fluoride group, and marrow cavity area was lower in the fluoride + K1 group (P < 0.05). In the L3 vertebral cancellous bone, bone volume, trabecular number and trabecular thickness were higher in the study groups than the control group (P < 0.05). Trabecular separation was reduced in the study groups (P < 0.05), and was lower in the fluoride + K1 group than the fluoride group (P < 0.05). The fluoride + K1 group had a significantly higher BMD than the other groups (P < 0.05), and the fluoride group had a significantly higher BMD than the control group (P < 0.05). The present study found that fluoride administration increased bone mass in both vertebrae and tibiae in growing rats. Simultaneous administration of vitamin K1 and fluoride resulted in an additional increase in vertebral bone mass. PMID- 19475761 TI - [The fine structure of enterochromaffin cells and their specific granules. Electron microscopic examination of the duodenum of guinea pigs]. PMID- 19475762 TI - [Flow in the mesenteric veins]. PMID- 19475763 TI - [Morphologic contributions to the back flow venous blood in the portal vein region]. PMID- 19475764 TI - Mentalization-based treatment for borderline personality disorder. A small, long term study concludes that this therapy is effective. PMID- 19475765 TI - Rare diseases offer insights into autism spectrum disorders. Preliminary laboratory studies suggest new biological targets for intervention. PMID- 19475766 TI - Yoga for anxiety and depression. Studies suggest that this practice modulates the stress response. PMID- 19475767 TI - Type 2 diabetes may slow thinking ability early on. PMID- 19475768 TI - More evidence on risks of antipsychotics in adults. Commentaries provide advice about putting the results in perspective. PMID- 19475769 TI - What is reminiscence therapy? PMID- 19475770 TI - Alzheimer's caregiving: day-to-day challenges. Bath time, mealtime, and bedtime are among the hardest parts of the day. Here are some ways to get through them. PMID- 19475771 TI - Arterial stiffness, hypertension, and rational use of nebivolol. AB - Arterial stiffness plays a key role in the pathophysiology of the cardiovascular system. Some indices of arterial stiffness (pulse wave velocity, augmentation index, characteristics of central blood pressure waveform) may be presently calculated and evaluated in the clinical setting. Age and blood pressure are the two major clinical determinants of increased arterial stiffness, while molecular determinants of arterial stiffness are related to fibrotic components of the extracellular matrix, mainly elastin, collagen and fibronectin. Increased arterial stiffness has been consistently observed in conditions such as hypertension, dyslipidemia and diabetes. Arterial stiffness evaluated by means of carotid-femoral pulse wave velocity yielded prognostic significance beyond and above traditional risk factors. A more favorable effect of calcium channel blockers, diuretics and ACE inhibitors compared with beta-blockers on indices of arterial stiffness was observed in several studies. It is conceivable that newer beta-blockers with additional vasodilating properties, such as nebivolol, which has favorable effects on carbohydrate and lipid metabolism, as well as on endothelial function and on oxidative stress, may have favorable effects on arterial stiffness, compared with atenolol. In fact, in recent studies, nebivolol was demonstrated to improve artery stiffness to a greater extent than older beta blockers. Because endothelial dysfunction and increased arterial stiffness play an important role in the early atherosclerotic processes and are associated with poor outcomes and increased mortality, independently of blood pressure, the ability of nebivolol to enhance release of endothelium-derived nitric oxide, and consequently improve endothelial function and arterial stiffness, may have significant clinical implications for the use of this agent in the treatment of hypertension and cardiovascular diseases. PMID- 19475772 TI - Retraction notice to "Surgery on the affected upper extremity of patients with a history of complex regional pain syndrome: the use of intravenous regional anesthesia with clonidine" [J Clin Anesth 16 (2004) 517-522]. PMID- 19475773 TI - Prevention of diabetes in hypertensive patients: results and implications from the VALUE trial. AB - A growing number of experimental and clinical studies have provided evidence indicating that pharmacological blockade of the renin-angiotensin system (RAS) by either angiotensin-converting enzyme inhibitors or angiotensin type 1 receptor blockers reduces the incidence of new onset type 2 diabetes in subjects with hypertension and/or cardiovascular disease, independently of antihypertensive and cardiovascular protective effects. The beneficial effects of RAS inhibition on the development of diabetes have been largely attributed to improvements in peripheral insulin sensitivity and glucose metabolism. This review focuses on recent experimental and clinical evidence supporting the role of RAS inhibition in the reduction of new onset type 2 diabetes and the mechanisms that may be involved. PMID- 19475774 TI - Efficacy, effectiveness and real life goal attainment of statins in managing cardiovascular risk. AB - Statins became available for the treatment of hypercholesterolemia in 1987. Multiple, well-designed, placebo-controlled, double-blind studies revealed that each 1% reduction in serum cholesterol level was associated with about 1% reduction in risk of cardiovascular events. Low-density lipoprotein (LDL) cholesterol reduction to less than 78 mg/dL may be associated with reduction of atheroma burden. Patients with high levels of high specificity C-reactive protein and having LDL cholesterol less than 3.4 mmol/L (130 mg/dL) in primary prevention settings benefited from aggressive LDL cholesterol reduction with rosuvastatin over a 2-year period. However, in real life practice, about half of patients who are prescribed statins discontinue the medication by the end of the year. Medication adherence is lower in younger patients, women, and absence of known coronary heart disease. Personal features of the prescribing physician and dispensing pharmacies also affect patients' compliance. More studies are needed to evaluate if "compliance packets" would benefit patients in a real life situation. PMID- 19475775 TI - Fixed combination of amlodipine and atorvastatin in cardiovascular risk management: patient perspectives. AB - Hypertension and dyslipidemia are two of the most commonly co-occurring cardiovascular risk factors which together cause an increase in coronary heart disease-related events that is more than simply additive for anticipated event rates with each condition. Data have shown that even relatively small reductions in both blood pressure and cholesterol levels can lead to large reductions in the risk for cardiovascular events. However, though there are robust data on the beneficial effect of concomitant reduction in these risk factors, the reality is that this is achieved in <10% of patients. There is nonadherence with prescribed therapies with up to 50% of patients stopping their medications of their own volition for a variety of reasons. There is a reasonable evidence base to suggest that simplifying drug regimens and reducing pill burden will enhance patient adherence. The fixed-dose combination containing the antihypertensive agent amlodipine besylate and the statin atorvastatin is the first combination of its kind, which is both efficacious and safe and could potentially improve medication compliance, thereby improving the outcomes in these patients. PMID- 19475776 TI - Safety and efficacy of rosiglitazone in the elderly diabetic patient. AB - Diabetes is an important health condition for the aging population; at least 20% of patients over the age of 65 years have diabetes, and this number can be expected to grow rapidly in the coming decades. Rosiglitazone, a drug in the thiazolidinedione class which targets insulin resistance, was approved by drug regulatory bodies based on its ability to improve glycemic control nearly ten years ago. The greatest long-term risk in diabetes is cardiovascular disease with macrovascular disease being the cause of as much as 80% of mortality. More recently the cardiovascular safety of rosiglitazone was brought to center stage following several meta-analyses and the unplanned interim analysis of the RECORD trial. As opposed to pioglitazone, current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. A thiazolidinedione class effect however seems apparent with respect to the increased risk for fractures and congestive heart failure. Clinical trial evidence on rosiglitazone therapy in the elderly is limited. The available evidence is mainly related to observational cohort studies. Most of the trial evidence relates to a younger population and therefore these data can not be directly extrapolated to an older population. The effects of the thiazolidinedione drug class remain incompletely understood. PMID- 19475777 TI - Safety and efficacy of alteplase in the treatment of acute ischemic stroke. AB - After publication of the results of the National Institute of Neurological Disorders and Stroke study, the application of intravenous thrombolysis for ischemic stroke was launched and has now been in use for more than 10 years. The approval of this drug represented only the first step of the therapeutic approach to this pathology. Despite proven efficacy, concerns remain regarding the safety of recombinant tissue-type plasminogen activator for acute ischemic stroke used in routine clinical practice. As a result, a small proportion of patients are currently treated with thrombolytic drugs. Several factors explain this situation: a limited therapeutic window, insufficient public knowledge of the warning signs for stroke, the small number of centers able to administer thrombolysis on a 24-hour basis and an excessive fear of hemorrhagic complications. The aim of this review is to explore the clinical efficacy of treatment with alteplase and consider the hemorrhagic risks. PMID- 19475778 TI - Choice of ACE inhibitor combinations in hypertensive patients with type 2 diabetes: update after recent clinical trials. AB - The diabetes epidemic continues to grow unabated, with a staggering toll in micro and macrovascular complications, disability, and death. Diabetes causes a two- to fourfold increase in the risk of cardiovascular disease, and represents the first cause of dialysis treatment both in the UK and the US. Concomitant hypertension doubles total mortality and stroke risk, triples the risk of coronary heart disease and significantly hastens the progression of microvascular complications, including diabetic nephropathy. Therefore, blood pressure reduction is of particular importance in preventing cardiovascular and renal outcomes. Successful antihypertensive treatment will often require a combination therapy, either with separate drugs or with fixed-dose combinations. Angiotensin converting enzyme (ACE) inhibitor plus diuretic combination therapy improves blood pressure control, counterbalances renin-angiotensin system activation due to diuretic therapy and reduces the risk of electrolyte alterations, obtaining at the same time synergistic antiproteinuric effects. ACE inhibitor plus calcium channel blocker provides a significant additive effect on blood pressure reduction, may have favorable metabolic effects and synergistically reduce proteinuria and the rate of decline in glomerular filtration rate, as evidenced by the GUARD trial. Finally, the recently published ACCOMPLISH trial showed that an ACE inhibitor/calcium channel blocker combination may be particularly useful in reducing cardiovascular outcomes in high-risk patients. The present review will focus on different ACE inhibitor combinations in the treatment of patients with type 2 diabetes mellitus and hypertension, in the light of recent clinical trials, including GUARD and ACCOMPLISH. PMID- 19475779 TI - Review of nifedipine GITS in the treatment of high risk patients with coronary artery disease and hypertension. AB - Nifedipine is a dihydropyridine calcium-channel blocker (CCB) introduced approximately 30 years ago for the prophylaxis of angina symptoms, and then later utilized as an anti-hypertensive agent. In the 1990s, several meta-analyses and a case-control study were published which raised concern regarding increased mortality and increased risk for myocardial infarction with short-acting nifedipine. Further evaluation of these meta-analyses and case control study underscores some important limitations and the need to further elucidate the role of this class of medications in high-risk patients. Until 2000, there was a paucity of data on the long-term effects as well as the long-term outcomes of CCBs in the treatment of stable coronary disease or in patients with manifestations of the disease such as hypertension or angina. While it has been well established that nifedipine and other dihydropyridines lower blood pressure and improve symptoms of angina, several studies were designed to evaluate the effect of dihydropyridines on "hard" outcomes, specifically cardiovascular and cerebrovascular events. In this review, we describe the clinical studies evaluating the use of nifedipine when compared to placebo as well as other anti hypertensive therapies in an attempt to identify the most appropriate place in therapy for this class of medications and to further clarify its utilization in high-risk patients. PMID- 19475784 TI - Mark-recapture estimation of a salmon smolt population. AB - A mark-recapture experiment was conducted applying a two-sample stratified technique to estimate the number of Atlantic salmon smolts, Salmo salar, migrating out of the Conne River, Newfoundland. We developed a model where parameters are introduced to describe the mean time for the salmon to migrate between the release site and recapture site and to describe the probability of capture on a particular date. The latter are then used to expand the number of untagged smolts captured to estimate the daily run sizes. We discuss the advantages of this new approach over other models. For example, this formulation allows great flexibility in the experimental design, is robust to violations of assumptions, and allows the influence of environmental factors upon the parameters to be investigated. PMID- 19475782 TI - Inhaled iloprost for the control of pulmonary hypertension. AB - Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an elevated pulmonary arterial pressure and vascular resistance with a poor prognosis. Various pulmonary and extrapulmonary causes are now recognized to exist separately from the idiopathic form of pulmonary hypertension. An imbalance in the presence of vasoconstrictors and vasodilators plays an important role in the pathophysiology of the disease, one example being the lack of prostacyclin. Prostacyclin and its analogues are potent vasodilators with antithrombotic, antiproliferative and anti-inflammatory qualities, all of which are important factors in the pathogenesis of precapillary pulmonary hypertension. Iloprost is a stable prostacyclin analogue available for intravenous and aerosolized application. Due to the severe side effects of intravenous administration, the use of inhaled iloprost has become a mainstay in PAH therapy. However, owing to the necessity for 6 to 9 inhalations a day, oral treatment is often preferred as a first-line therapy. Numerous studies proving the efficacy and safety of inhaled iloprost have been performed. It is therefore available for a first-line therapy for PAH. The combination with endothelin-receptor antagonists or sildenafil has shown encouraging effects. Further studies with larger patient populations will have to demonstrate the use of combination therapy for long-term treatment of pulmonary hypertension. PMID- 19475785 TI - Forecasting age-related macular degeneration through 2050. PMID- 19475781 TI - Role of aliskiren in cardio-renal protection and use in hypertensives with multiple risk factors. AB - The renin-angiotensin-aldosterone system (RAAS) is an important mediator of blood pressure (BP) and volume regulation in both normotensive and hypertensive persons and is a major contributor to hypertension-related target organ damage. The concept of renin inhibition for managing hypertension by blocking the RAAS pathway at its point of activation is very attractive since the renin angiotensinogen reaction is the first and rate-limiting step in the generation of angiotensin II (Ang II). Aliskiren, the first in a new class of orally effective direct renin inhibitors (DRIs), is approved for the treatment of hypertension. It is effective in reducing BP in the general population of hypertensive patients and in special patient groups such as obese persons, and has a tolerability and safety profile similar to placebo. Aliskiren has renoprotective, cardioprotective and anti-atherosclerotic effects in animal models that appear to be independent of BP lowering. It reduces proteinuria in diabetic patients and has favorable neurohumoral effects in patients with symptomatic heart failure. Additional outcome trials are needed to establish the role of this novel class of antihypertensive medication in the therapeutic armamentarium. PMID- 19475783 TI - Improving outcomes in patients undergoing percutaneous coronary intervention: role of prasugrel. AB - Dual oral antiplatelet therapy, aspirin plus thienopyridine, has permitted a rapid increase in the use of coronary intervention procedures. Clopidogrel is the thienopyridine of choice for dual antiplatelet therapy in patients treated with percutaneous coronary intervention. However, there are two issues with clopidogrel: (1) clopidogrel's antiplatelet activity is delayed because the drug needs to be metabolized into its active form and (2) variability in patient response to clopidogrel has been demonstrated. To overcome these shortcomings of clopidogrel, new more potent inhibitors of P2Y12 receptors, which have a more rapid onset of action have been introduced for clinical evaluation. This article is a nonexhaustive review of the literature and concentrates on prasugrel, a third-generation, oral thienopyridine. The purpose is to summarize the current knowledge about the benefits and risks of prasugrel and to outline the most prudent strategies for the drug's clinical use. PMID- 19475786 TI - Preparation for a pandemic: influenza A H1N1. PMID- 19475787 TI - Special issue: A symposium honoring the lifetime achievements of Prof Calvin W. Schwabe. PMID- 19475788 TI - Proceedings of the XIII International Symposium on Intracranial Pressure and Brain Monitoring, July 22-26, 2007, San Francisco, California, USA. PMID- 19475780 TI - The use of sibutramine in the management of obesity and related disorders: an update. AB - AIMS: To review the major trials that evaluated the efficacy and safety of the use of sibutramine for weight loss and the impact of this agent on obesity related disorders. METHODS AND RESULTS: The most important articles on sibutramine up to January 2009 were located by a PubMed and Medline search. Sibutramine reduces food intake and body weight more than placebo and has positive effects on the lipid profile (mainly triglycerides and high density lipoprotein cholesterol), glycemic control and inflammatory markers in studies for up to one year. Preliminary studies showed that sibutramine may also improve other obesity-associated disorders such as polycystic ovary syndrome, left ventricular hypertrophy, binge eating disorder and adolescent obesity. The high discontinuation rates and some safety issues mainly due to the increase in blood pressure and pulse rate have to be considered. Additionally, it has not yet been established that treatment with sibutramine will reduce cardiovascular events and total mortality. CONCLUSIONS: Sibutramine, in conjunction with lifestyle measures, is a useful drug for reducing body weight and improving associated cardiometabolic risk factors and obesity-related disorders. Studies of longer duration are required to determine the precise indications of the drug, to evaluate safety issues and to assess its efficacy on cardiovascular mortality. PMID- 19475790 TI - A measure of compassion. PMID- 19475789 TI - Treating allergic rhinitis: continuous versus on-demand regime? Executive summary of the Supportive Initiatives for the Global Management of Allergy (SIGMA): report from the Belgian Working Group. AB - This Supportive Initiative for the Global Management of Allergy (SIGMA) initiative gathered together four multidisciplinary and inter-university groups of Belgian experts in the treatment of allergic rhinitis to review the literature and come to a consensus opinion on the global management of allergy. Their conclusions were as follows. Group 1 concluded that in children suffering from allergic rhinitis, there is sufficient expert opinion in favour of continuous treatment with both H1-antihistamines and corticosteroids for controlling symptoms during periods of allergen exposure, but not to support continuous treatment during periods when symptoms are negligible in an attempt to prevent the development of new allergic diseases. Group 2 came to similar conclusions in adults. Group 3 considered adults with concomitant asthma and stressed the crucial necessity to screen each asthmatic for allergic rhinitis and institute appropriate therapy for both conditions. Even though efficacious treatment algorithms are available for both rhinitis and asthma, an integrated management of these frequently concomitant diseases is not always prescribed even though there is a proven clinical advantage of adequate treatment of the nose of asthmatics. Group 4 concluded that for both H1-antihistamines and nasal corticosteroids, safety data indicate that continuous treatment may be given without fears of adverse consequences. With regard to the cost implications of continuous therapy versus on-demand therapy, there are indications that effective treatment of allergic rhinitis by continuous treatment reduces overall drug costs, particularly that of escape medication and indirect costs in the form of days absent from work and school. PMID- 19475791 TI - CPR decisions in palliative care should allow for a good death. PMID- 19475792 TI - Making effective use of predicted discharge dates to reduce the length of stay in hospital. AB - This article outlines an initiative by nursing staff in the elective orthopaedic department at Cardiff and Vale NHS Trust to improve discharge planning for all patients on the ward. It describes how renewed focus on the predicted discharge date among multidisciplinary teams and patients themselves increased the proportion of patients who went home by or before their target date and reduced the average length of stay. PMID- 19475793 TI - Exploring how to ensure compassionate care in hospital to improve patient experience. AB - This article is the first in a series by the King's Fund Point of Care programme looking at practical interventions to improve patients' experiences of care. It discusses what compassion means, what might prevent consistent compassionate care and what practical changes could ensure compassion. PMID- 19475794 TI - Palliative care 3: using palliative nursing skills in clinical practice. AB - Implementing a philosophy of care which emphasises quality of life, holism, futility and family involvement and sees death as a natural end of life is an enormous challenge for nurses in current complex healthcare environments. This article explores the practice-based reality of using the palliative approach in multiple settings and the challenges in such care. PMID- 19475795 TI - What dressing should be used under compression bandages or does it not matter? PMID- 19475796 TI - Using sympathomimetic drugs to manage hypotension 2: use in clinical practice. AB - The second in this two-part unit on sympathomimetic drugs discusses their use in clinical practice with certain patient groups. Part 1 outlined background information on the cardiovascular system and how its various components affect blood pressure. PMID- 19475797 TI - Within these walls. PMID- 19475798 TI - The new face of public protection. PMID- 19475799 TI - Apprenticeships can beat the downturn. PMID- 19475800 TI - All in the mind. PMID- 19475801 TI - On getting ready for an all-graduate profession. PMID- 19475802 TI - Setting our course. PMID- 19475803 TI - Culturally competent care complements interactions with people with disabilities. AB - This article describes the concept of disability as a culture, discusses key components of cross-cultural communication with people with disabilities, and identifies the key elements of providing culturally competent care to people with disabilities. To gain an understanding of cultural competence, it is important to understand the concepts and definitions of culture, disability, and competence. The World Health Organization classification of functioning, disability, and health will be used as the theoretical model in the discussion on disability. J. Campinha-Bacote's Cultural Competent Model of Care is used as the theoretical model for the discussion on cultural competence. PMID- 19475804 TI - Stress response in female veterans: an allostatic perspective. AB - Women serving in the military face many sources of stress, such as separation from home and family, sexual harassment and assault, and deployment to traumatic war zones. Some women are vulnerable to the effects of these stressors, resulting in deleterious mental and physical health outcomes. Understanding these risks through the theoretical model of allostasis can help identify those who will be most vulnerable and help healthcare providers prevent some negative outcomes and improve rehabilitation for some women when they return stateside. Women may be more likely than men to present with mental health problems such as posttraumatic stress disorder and depression after military service. They also may be at increased risk, based on their war-zone stress response, for disparate illness such as medically unexplained illness, cancer, and heart disease. The need for care for these women is expected to increase as more women are deployed to conflicts. PMID- 19475805 TI - Nurse-managed free clinic fosters care connection for homeless population. AB - The goal of this article is to demystify the process that healthcare providers must follow when working with homeless patients who sustain injuries or exhibit illnesses that necessitate rehabilitation care. Observations made over a period of more than 12 years at an inner-city medical/psychiatric nurse-managed free clinic that delivers cutting-edge services and educates multidisciplinary students to care for disenfranchised populations led the author to several conclusions: homeless people frequently lose their identity as individuals when facing healthcare providers; previous negative perceptions of homelessness can turn positive when care providers meet these patients on a person-to-person level; the concept of health and rehabilitation must be clearly understood in the same way by both providers and patients for nursing goals to be realistic and achievable; and a collaborative relationship must be formed between nurses and patients. PMID- 19475807 TI - The potential of disease management for neuromuscular hereditary disorders. AB - Neuromuscular hereditary disorders require long-term multidisciplinary rehabilitation management. Although the need for coordinated healthcare management has long been recognized, most neuromuscular disorders are still lacking clinical guidelines about their long-term management and structured evaluation plan with associated services. One of the most prevalent adult-onset neuromuscular disorders, myotonic dystrophy type 1, generally presents several comorbidities and a variable clinical picture, making management a constant challenge. This article presents a healthcare follow-up plan and proposes a nursing case management within a disease management program as an innovative and promising approach. This disease management program and model consists of eight components including population identification processes, evidence-based practice guidelines, collaborative practice, patient self-management education, and process outcomes evaluation (Disease Management Association of America, 2004). It is believed to have the potential to significantly improve healthcare management for neuromuscular hereditary disorders and will prove useful to nurses delivering and organizing services for this population. PMID- 19475806 TI - Don't worry, be positive: improving functional recovery 1 year after hip fracture. AB - It is not uncommon for studies examining factors associated with functional recovery 1 year after hip fracture to be presented from the perspective of clinicians or researchers. Few studies have examined factors that facilitate functional recovery from the patient's perspective. This article discusses community-dwelling older adults age 65 and older who sustained a hip fracture and received surgical repair and postacute rehabilitation. Data were collected 1 year after postacute rehabilitation. Content analysis was used for the descriptive study. Participants reported that rehabilitation services greatly facilitated their recovery. Participants also recognized the importance of their own motivation, and noted it was essential to maintain a positive attitude and fully engage in recommended rehabilitation activities. The keys to functional recovery were active participation in rehabilitation and following instructions from care providers. In addition, self-determination, a positive attitude, and social support played significant roles in making rehabilitation work. PMID- 19475809 TI - "The art of medicine". PMID- 19475808 TI - 24-hour rehabilitation nursing: the proof is in the documentation. AB - For a facility to be classified as an inpatient rehabilitation facility (IRF), Medicare requires that the facility provide 24-hour rehabilitation nursing. Documentation is important because it helps determine the most appropriate site for the provision of care. Functional assessments are ongoing and should provide information about patients and which interventions are most appropriate; this allows for successful achievement of rehabilitation goals. Nurses must define the elements of a quality assessment based on the individual patient and then monitor findings and respond appropriately. Reimbursement is supported by measuring functional outcomes based on the initial assessment of patients. The final reimbursement, based on possible denial of a claim, is supported by documentation of the functional outcome in the medical record. Medicare contractors cannot observe the everyday interventions nurses use with patients, so they require documentation as proof. This article features examples of documentation that nurses can use to help meet the expectation of 24-hour nursing. Following through with these suggestions will not only help provide proof of 24-hour nursing, more accurate reimbursement, and the security of a full reimbursement, but ultimately will ensure quality rehabilitation services and care for patients. PMID- 19475810 TI - Bad result and slow reaction. PMID- 19475811 TI - Time is brain. Stroke--like trauma--demands immediate, definitive treatment. PMID- 19475812 TI - Tailoring care for elderly outliers: more questions than answers. PMID- 19475813 TI - von Willebrand disease, pregnancy and neuraxial anesthesia: a multi-disciplinary approach for successful regional anesthesia. AB - Fearing the devastating neurological complications in a parturient with the von Willebrand disease secondary to paucity of studies defining the guidelines to assess the risk of bleeding complications, anesthesiologists are often reluctant to administer neuroaxial anesthesia. We present a case report of a parturient with type I von Willebrand disease who presented for induction of labor at 39 weeks of gestation. After consultation with the hematologist well ahead of the conception, appropriate laboratory workup including clotting factor levels including FVIII, vWF:RcoF, vWF:Ag on different occasions peripartum, and provision of adequate prophylactic medical treatment, she underwent Cesarean section under epidural anesthesia without neurological or bleeding complications. von Willebrand disease is the most common inherited bleeding disorder that may result in various bleeding complications in a parturient as a result of hemostatic challenges during pregnancy. Yet the recommendations are based on anecdotal observations of the authors of small case series and surveys. Our case report emphasizes the importance of advanced planning, careful patient assessment, and multi-disciplinary team approach for the successful regional anesthesia as suggested by the guidelines based on clinical experiences. PMID- 19475814 TI - Spatially fractionated (GRID) therapy for large and bulky tumors. AB - Avanced bulky tumors warrant aggressive therapy to attempt to maximize local control of the disease. Spatially fractionated radiation therapy (GRID) delivers a single-fraction of high dose radiation to these tumors with a curative or palliative goal. GRID therapy may be combined with fractionated radiation therapy or used in a therapeutic multi-modality setting to achieve control of the bulky disease. Current clinical data confirms the value of GRID therapy in the management of large volume of disease with an acceptable toxicity profile. GRID therapy has broad systemic effects leading to increases in a variety of cytokines that correlate with clinical outcome. PMID- 19475821 TI - [Wounds in the elderly and very elderly]. PMID- 19475823 TI - [Living with HIV today]. PMID- 19475822 TI - [The paravertebral block for postoperative pain in thoracic surgery]. PMID- 19475824 TI - [Epidemiology, physiopathology and therapeutic modalities of HIV infections]. PMID- 19475826 TI - [Listening to patients for better care]. PMID- 19475827 TI - [Therapeutic education of the patient infected with HIV]. PMID- 19475825 TI - [Chronicity of HIV infections, a persistent evolution]. PMID- 19475829 TI - [Maternal-fetal transmission of HIV and after care of infants in pediatrics]. PMID- 19475830 TI - [Seropositive mother, a daily challenge]. PMID- 19475828 TI - [Long term management of HIV and anal cancer]. PMID- 19475831 TI - [Aide associations for surviving HIV in an exile situation]. PMID- 19475832 TI - [HIV and professional risk]. PMID- 19475834 TI - [New therapies in the management of seropositive persons]. PMID- 19475833 TI - [Palliative care and HIV]. PMID- 19475835 TI - [3/10. The competence-based approach]. PMID- 19475836 TI - [4/5. Nurse/nurse's aide collaboration in drug distribution]. PMID- 19475837 TI - [International multicentre studies, inter-cohort analyses, unsustainable proliferation of authorship. Are these the expected answers to face HIV disease?]. AB - The most recent evidences on HIV infection have been obtained through large multicentre trials, or intercohort analyses including patients enrolled by hundreds of investigators-coinvestigators around the world. While extensively pooled data are needed to assess infrequent events (proportionally rare toxicity), long-term end-points (like mortality), or to perform efficacy or non inferiority comparisons between different therapeutic strategies, relevant biases distorsions descending from the extremely elevated number of enrolling centers and sperimentators are expected, while the full report among quoted co-authors of all investigators and co-investigators supports an unacceptable number of presumptive authors of each paper, ranging from hundreds to over one thousand. PMID- 19475838 TI - [Relationship between atrial fibrillation and other cardiovascular risk factors in Alzheimer's disease. New prevention opportunities]. AB - Dementia is one of the most frequent neurological disorders in the elderly. Several vascular risk factors such as atrial fibrillation have been found to be associated with vascular dementia and Alzheimer's disease. Early interventions at reducing atrial fibrillation may have a strong impact on future incidence and prevalence of cognitive impairment. PMID- 19475839 TI - [Evidences on the relationship between Mediterranean diet and health status]. AB - Mediterranean diet (MD) is an eating pattern that has been worldwide promoted as a model for healthy eating and has been reported to contribute to a favourable health status and to a better quality of life. Over the last years, despite evidences on the beneficial effects of the single components of MD have been reported, research interest has been focused on the whole dietary pattern rather than on a single nutrient, since individual analyses of nutrients and food can ignore important interactions between components of a diet and, more importantly, because people do not eat isolated nutrients. Therefore, dietary scores estimating the adherence to the MD have been operationalised and have been found to be associated with a reduction of overall mortality, cardiovascular diseases, hypertension and obesity. Furthermore, a high degree of adherence to MD has been found related to lower concentrations of inflammation, endothelial dysfunction and coagulation markers. In a recent meta-analysis on over than 1,5 million of persons we were able to demonstrate that a higher adherence to Mediterranean diet is associated with a significant reduced risk of incidence and mortality from all causes and from cardiovascular, neoplastic and neurodegenerative diseases. PMID- 19475841 TI - [Hypokalemia from ectopic ACTH secretion and hypothiroidism in patient affected by small cell lung cancer]. AB - Endocrin paraneoplastic syndromes are characterized by an ectopic hormonal production. The ectopic adrenocorticotropic hormone (ACTH) secretion is often associated with small cell lung cancer. We report the case of 64-years-old man with persistent hypokalemia in Cushing's syndrome due to ectopic ACTH secretion. The patient was affected by small cell lung cancer and presented an hypothiroidism too. A proper chemotherapy resulted in remission of the hypokalemia, but the hypothiroidism was not influenced during our observation period. PMID- 19475840 TI - [Dilated cardiomyopathy post-chemotherapy]. AB - We describe the case of a dilated cardiomyopathy with angiographically normal coronary arteries in a 32-year-old man who underwent head and spine radiotherapy and high dose antracicline chemotherapy at the age of 5 year for acute lymphoblastic leukemia. The long-term detrimental cytotoxic effect of remote life saving chemotherapy should be considered in survivals of leukemia. PMID- 19475842 TI - [Organic nitrates: still interesting after all these years]. AB - Organic nitrates remain among the oldest and most commonly employed drugs in cardiology. Despite that, the mechanisms of action, pharmacology, and, most importantly, side effects, were described only recently. We believe that all physicians should be aware of these lines of evidence. Further studies are necessary to evaluate the impact of nitrate therapy on mortality and morbidity. Paradoxically, more than 150 years after introduction in the market, these data are not yet available. The present review focuses on the recent findings in this field and on future lines of research. PMID- 19475843 TI - [Physiopathology and possible clinical use of hematopoietic stem cells. Recent advances]. AB - Studies carried out during these last years have lead to a considerable improvement in the understanding of the biology of hematopoietic stem cells. The development of hematopoietic stem cell transplantation had a considerable impact on the therapy of leukemias. The improvement in transplantation protocols allowed the development of allogenic transplantations in which the graft versus tumor contributes to the anti-tumor effects. In parallel many growth factors acting on hematopoietic cells have been isolated and used in clinic to stimulate hematopoietic recovery and stem cell mobilization. Finally, malignant stem cells have been isolated and characterized in acute and chronic leukemias: these cells are responsible for the development and maintenance of the leukemic process and must be eradicated to obtain an effective treatment of leukemias. PMID- 19475844 TI - [Inspecting the throat of a young colleague. Cleft uvula]. PMID- 19475845 TI - [DEGAM criticizes the established immunization committee. "A large number of immunization recommendations need testing" (interview by Dr. Thomas Meissner)]. PMID- 19475846 TI - [STIKO member holds arguments unfounded. "Immunization fatigue is not the sequela of the many vaccinations"]. PMID- 19475847 TI - [Self assessment of 920 physician assistants. High qualifications, but in IGel work has deficits]. PMID- 19475849 TI - [Fatalities in athletes. How can we protect our athletes? (interview by Dr. Jochen Aumiller)]. PMID- 19475848 TI - [Doping in the next generation: wringing extra performance from the genotype]. PMID- 19475850 TI - [Critical limb ischemia: here not just the leg is at risk]. PMID- 19475851 TI - [Forensic medicine and prevention are not contradictions. "Victim medicine" moves into the spotlight]. PMID- 19475852 TI - [Certification of death by the family doctor: frequent mistakes and consequences]. PMID- 19475853 TI - [Physical child abuse: suspicious facts and judical implications]. PMID- 19475854 TI - [Use of short acting sedatives: how to minimise forensic risks]. PMID- 19475855 TI - [Unnecessary operations can be prevented. Thyroid check for every patient over 40 years of age]. PMID- 19475856 TI - [Prescribing levothyroxine. Preparation hopping risks accurate regulation]. PMID- 19475857 TI - [Broken glass injuries: does every splinter have to be removed?]. PMID- 19475858 TI - [Emergency checklist: hordeolum]. PMID- 19475859 TI - [2008--The year of the big studies about the therapy of type-2-diabetes. ACCORD, ADVANCE, VADT, and the UKPDS 10-year follow-up data]. PMID- 19475860 TI - [Oral anticoagulation. What is vital in blood coagulation management? (interview by Dr. Judith Neumaier)]. PMID- 19475861 TI - [What is the normal fetal weight?]. PMID- 19475862 TI - [Extensive neonatal heel injection screening for metabolic diseases in the Netherlands]. PMID- 19475863 TI - [Sickle cell disease in heel injection screening. I]. PMID- 19475864 TI - [Sickle cell disease in heel injection screening. II]. PMID- 19475865 TI - [Musical hallucinations]. PMID- 19475866 TI - [Systematic reviews, an update]. PMID- 19475867 TI - [Experimental therapy in Duchenne muscular dystrophy]. PMID- 19475868 TI - [Pinched peroneal superficialis nerve]. PMID- 19475870 TI - [Burn wounds in neonates caused by hot warming bottles]. PMID- 19475871 TI - [Diagnostic images (417) A girl with a 'tail' Lumbosacral hypertrichosis (faun tail)]. PMID- 19475872 TI - [Bankruptcy threat hospitals is bad for care]. PMID- 19475873 TI - [The BEAUTIFUL study]. PMID- 19475874 TI - [Three good reasons to perform a postmortem examination in all cases of juvenile sudden death]. AB - The aim of this review is to underline the reasons why a post-mortem examination has to be performed in all cases of juvenile sudden death. Sudden death in children and young adults can be caused by potentially heritable cardiovascular disorders and fatal outcome is often the first symptom in apparently healthy subjects. In these cases, a careful autopsy, performed according to a standardized protocol, becomes the sole diagnostic tool to guide clinical and molecular genetic family screening and to adopt the proper therapeutic and preventive strategies. Thus, a post-mortem examination is a fundamental part of a multidisciplinary approach to the issue of juvenile sudden death. PMID- 19475875 TI - [Assessment of quality of life in patients with peripheral arterial disease: a problem left ahead]. AB - Peripheral arterial disease is a common clinical condition and represents a manifestation of systemic atherosclerosis. It has been demonstrated that peripheral arterial disease impairs significantly quality of life, and thus its improvement has become an important goal of therapy, particularly in symptomatic patients. In addition, the impact of this disease on quality of life is not adequately described by physical examination findings and common clinical data, such as the ankle-brachial index. Thus, to properly understand the clinical evolution of peripheral arterial disease and its treatment, it is useful to integrate clinical outcome measures with data derived from the patient's point of view in order to avoid that procedural success is evaluated only in terms of appropriate use of the available technical tools and of a good angiographic result without taking into account its consequences on daily future life of patients. It would therefore be necessary that the caregivers involved in the evaluation and treatment of patients with peripheral arterial disease are able to use and interpret the validated instruments for quality of life assessment. Among therapeutic strategies, percutaneous transluminal angioplasty is emerging as a suitable option to improve both clinical outcome and quality of life, even though it cannot contrast the progression of atherosclerotic disease. In this article we review major generic and specific instruments to assess patient-reported quality of life. Moreover, we describe the impact of peripheral arterial disease and its endovascular treatment on quality of life. PMID- 19475876 TI - [Percutaneous transluminal angioplasty: synonymous of quality of life?]. PMID- 19475877 TI - [Myocardial injury in carbon monoxide poisoning]. AB - Carbon monoxide (CO) intoxication is the most common cause of accidental poisoning in developed countries and, although most published data relate to its neurological manifestations, it often leads to cardiac damage. Myocardial hypoxia due to the formation of carboxyhemoglobin is not enough to explain such damage fully as a major role is played by the direct effect of CO on the heart as a result of the reversible inhibition of mitochondrial respiration and oxidative stress. Cardiac damage secondary to CO poisoning can be detected not only in patients with known ischemic heart disease but also in subjects with undamaged coronary arteries. Given the wide range of cardiovascular manifestations (the entity of which is related to the severity of intoxication), useful information can be obtained by carefully recording the patient's medical history, analyzing electrocardiographic alterations, and determining the biochemical markers of cardiac necrosis. Moreover, echocardiographic examination may highlight the extent of the alterations in left ventricular function due to myocardial stunning associated with CO intoxication and evaluate its evolution over time. Clinical studies suggest that all patients admitted to hospital with moderate to severe CO poisoning should routinely undergo ECG and serial evaluation of cardiac markers, and that those with positive signs of myocardial cytonecrosis or preexisting ischemic heart disease should also undergo echocardiography. A finding of myocardial damage in patients with CO poisoning seems to indicate an unfavorable long-term prognosis, although it needs further confirmation. PMID- 19475878 TI - [Migration flow and imported diseases: chronic chagasic cardiomyopathy]. AB - Chagas disease, caused by the parasite Trypanosoma cruzi, is transmitted by triatomine bugs in endemic regions of the American continent and less frequently by blood transfusion and congenital transmission. Immigration rates explain why the disease can be found worldwide. Non-endemic countries that receive a significant amount of Latin American immigrants should be familiarized with the disease to allow prevention, diagnosis and early treatment. In Italy, where no serologic screening is routinely performed to detect Trypanosoma cruzi in blood donations, a special consideration must be held. Accordingly, attention to congenital transmissions of the disease should be drawn considering the lack of newborn screening. Though commonly unrecognized, chronic chagasic cardiomyopathy is the most common type of chronic myocarditis in the world. PMID- 19475879 TI - [Adherence to cardioprotective medications in coronary heart disease]. AB - Treatment of patients with ischemic heart disease relies on evidence-based medications such as beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, aspirin and statins, which are considered cornerstones to control symptoms, improve quality of life, reduce future events, and prolong survival. In spite of the clear benefits of therapy, previous studies have shown differences between the large randomized populations and the "real world" about long-term treatment in terms of efficacy, tolerability, costs, side effects and drug interactions. Moreover, a different awareness of the patient's compliance has been highlighted in relation to the setting (hospital, family doctor, etc.). The analysis and assessment of the prescription and efficacy of therapy for secondary prevention of coronary artery disease represent one of the most important challenges for the healthcare system, because reliable data are necessary to verify usefulness and results of therapy, prescribed at discharge after an acute coronary syndrome and/or coronary artery bypass graft, but above all the actual application of treatments should be pursued in every clinical setting. The Cardiology School of the Trieste University has constituted a working group of cardiology students that during the year 2009 will enroll and follow for 1 year all patients with coronary artery disease discharged from the Cardiovascular Department and Emergency Unit of the University Hospital of Trieste to assess: (1) if evidence-based medicine for secondary prevention of coronary artery disease is applied in the Trieste area; (2) adherence to prescribed treatment; (3) factors that are associated with non-adherence and consequences of non-adherence. PMID- 19475880 TI - [How to increase patient knowledge of their coronary heart disease: impact of an educational meeting led by nurses]. AB - BACKGROUND: Most patients discharged after an acute coronary event or a coronary revascularization do not have adequate knowledge of the nature of their disease and of the importance of a correct lifestyle. The aim of this study was to assess the effectiveness of an educational intervention led by nurses for patients admitted to hospital for coronary heart disease (CHD). METHODS: Since May 2003, regular health education meetings for inpatients with CHD and their relatives have been held by the nurses of the Cardiology Division of the Desio hospital. The topics covered are the nature of CHD, its risk factors and the prevention of recurrences. Before and after the meeting, a questionnaire is administered to explore patients' level of knowledge. RESULTS: From May 2003 to September 2004, 201 patients attended the meetings (151 men and 50 women, aged from 37 to 89 years). The majority (n=152, 76%) were admitted for an acute coronary syndrome. Attendance at the meeting significantly increased the patients' understanding of atherosclerosis (from 44 to 85%, p < 0.0001), coronary vessel function (from 56 to 92%, p < 0.0001) and the causes of cardiac necrosis or ischemia (from 58 to 88%, p < 0.0001). Their awareness of the importance of correct lifestyles increased, especially the number of patients willing to increase fruit and vegetable consumption (from 56 to 77%, p < 0.0001) or to increase physical activity (from 51 to 69%, p < 0.0001) to avoid a recurrence. CONCLUSIONS: A health education meeting organized by nurses for patients admitted for CHD improves their knowledge of their illness and awareness of the benefits of correct lifestyles to prevent worsening of their disease. PMID- 19475881 TI - [Knowledge as a tool for a more efficacious therapeutic approach in secondary prevention]. PMID- 19475882 TI - [Myocardial and cerebral infarction as initial presentation of antiphospholipid syndrome]. AB - The antiphospholipid antibody syndrome is the most common acquired thrombophilia; it is a systemic autoimmune disease characterized by recurrent arterial and venous thrombosis and/or pregnancy loss, in association with circulating antiphospholipid antibodies. The pathogenic mechanisms in antiphospholipid antibody syndrome that lead to in vivo injury are incompletely understood. Like other autoimmune diseases, a combination of genetic and environmental factors is involved. We report the case of a 50-year-old woman suffering from an antero lateral non-ST-elevation myocardial infarction. After few days, coronary angiography showed a severe occlusive arterial disease, involving anterior descending, circumflex e right coronary arteries. Percutaneous coronary intervention was performed with the implantation of a drug-eluting stent in the proximal segment of the anterior descending coronary artery. One day after discharge (10 days after the first hospitalization) the patient experienced dizziness, nausea, vomiting, swelling in absence of any electrocardiographic abnormalities or myocardial enzyme elevation; then she was hospitalized in the neurology department. Because of a similar episode, urgent cerebral computed tomography scan was performed 5 days later; it revealed two different acute ischemic areas, parietal in the right hemisphere and cerebellar in the left hemisphere. The diagnosis of antiphospholipid antibody syndrome was confirmed by high anticardiolipin antibody titers, also present in medium titer at 5 and 17 weeks apart. She was discharged without any sequelae, on warfarin and double antiplatelet therapy (aspirin and clopidogrel for 6 months), then warfarin and aspirin. PMID- 19475883 TI - [Tetralogy of Fallot with coronary-to-pulmonary artery fistula: a diagnostic snare]. AB - An 11-month-old infant, moderately cyanotic, with diagnosis of tetralogy of Fallot underwent corrective surgery. At echocardiographic evaluation, a subatretic right ventricular outflow tract without aortopulmonary collateral arteries, confluent pulmonary arteries and normal coronary pattern were evidenced. During operation, an undiagnosed large coronary-to-pulmonary artery fistula was disclosed. Because of the large variety of aortopulmonary collateral arteries that can be associated with this pathology, further imaging study is mandatory when oxygen saturation does not match the right ventricular outflow tract obstruction severity. PMID- 19475884 TI - [A new type of "tracing" for cardiologists?]. PMID- 19475885 TI - Placental findings in pregnancy-associated haemolytic uremic syndrome: clinicomorphological study of three cases. AB - Acute renal failure occurring in pregnancy or postpartum is often associated with preeclampsia, HELLP syndrome or haemolytic uremic syndrome: differential diagnosis may be difficult due to the overlapping symptoms of these syndromes. We report our experience on diagnosis, management and outcome of women with pregnancy associated haemolytic uremic syndrome, focusing on placental features. PMID- 19475886 TI - Fluorescent cytogenetics of renal cell neoplasms. AB - Renal cell neoplasms are a heterogeneous group of tumours in terms of pathological features and prognostic behaviour. The genetics of these tumours may aid in correct diagnosis and accurate assessment of prognosis. In ambiguous cases it may be necessary to utilise new markers that are capable of further discerning renal cell neoplasms. Fluorescence in situ hybridization (FISH) on formalin fixed, paraffin-embedded tissue is an increasingly useful technique in the detection of many diagnostic chromosomal abnormalities, among which chromosomes 1, 2, 3p, 6, 7, 10, 17 and Y are the most common. The addition of FISH to histological evaluation improves the diagnostic accuracy of core biopsies from renal masses, which may have an important impact in clinical management of many cases due to newer therapeutic approaches, including cryo- or radiofrequency ablation, nephron-sparing surgeries and target therapies. PMID- 19475887 TI - Application of liquid-based preparation to non-gynaecologic exfoliative cytology. AB - Thin-layer cytology (TLC) is an automated method for processing cells harvested in a liquid solution and collected onto a single slide. The leftover material can be used for other techniques such as immunocytochemistry, molecular biology and flow cytometry. TLC has been applied with good results in exfoliative cytology of pulmonary, urinary, gastrointestinal and oral districts as well as in the evaluation of serous effusions. The main advantages of TLC over conventional techniques (CS) are: (a) simplification of the sampling technique; (b) decrease in cellular artefacts leading to a lesser amount of inadequate diagnoses; and (c) applicability of additional investigations. The limits of TLC are: (a) changes in the morphologic picture of some lesions; (b) increase of the workload for technical staff; and (c) increased cost. The application of TLC to non gynaecologic specimens favours many innovative developments and can be regarded as an appropriate substitute for CS. PMID- 19475888 TI - Carcinoma of eyelid sebaceous glands: a case report. AB - The authors present a case of a rare tumour of the eyelid sebaceous glands with an unfavourable prognosis, and emphasize the importance of carrying out histological examination of all eyelid neoformations to better identify the lesion and obtain an accurate diagnosis. The Authors discuss the histopathologic aspects of this case, and the findings in the literature. PMID- 19475889 TI - Retroperitonial liposarcoma mimicking pheochromocytoma. AB - The authors report the case of a 46-year-old woman who presented with a 4 month history of paroxystic and recent hypertension accompagned by headaches, tachycardia and sweating. The patient had decreased appetite with epigastric discomfort and abdominal distension. Physical examination was initially normal with mainly normal tension and no abdominal or lombar mass in palpation. While hospitalised, she developed paroxystic crisis of flush, headaches and hypertension of 190/100 mmHg. Biological findings revealed hypokaliemia and normal kaliuria on 3 day samples, with normal glycaemia and normal creatininaemia. Hormonal investigation revealed elevated metanephrines (3 mg/24 hours). Magnetic resonance imaging showed an 11 cm x 8.5 cm retroperitoneal mass with an enhanced signal in T2, a hypotrophic non-functional left kidney and no adrenal adenoma. Clinical and hormonal features suggested a diagnosis of pheochromocytoma. After preoperative medication, open excision, including left radical nephrectomy and adrenalectomy, normalized the catecholamine urinary level, resolved hypokalemia, and improved hypertension. Pathologic examination revealed a well-differentiated liposarcoma, without any pheochromocytoma component, and left adrenal hyperplasia. The tumour cells were immunonegative for chromogranin A. No metastatic lesion was identified by thoraco-abdominal computed tomography. PMID- 19475890 TI - Primary umbilical endometriosis: a rare variant of extragenital endometriosis. AB - Endometriosis is defined as the presence of extra-uterine endometrial tissue. The prevalence rate of umbilical endometriosis ranges from 0.5 to 1.0% of all patients with extragenital endometriosis. In this report, we present a case of primary umbilical endometriosis to highlight the challenges encountered during diagnosis. A nulliparous 39-year-old woman presented to our department with a 2 year history of a tender, painful and non-reducible, firm umbilical mass that enlarged slowly reaching 2 cm in diameter. She had never been pregnant nor had any abdominal surgery. There was no sequential bleeding. Ultrasound of the umbilical region showed a well defined, oval shaped anechoic area. Histological examination on a cutaneous biopsy concluded umbilical endometriosis. The patient was subsequently referred to a gynecologist and underwent surgery with en bloc excision of the lesion. Generally, umbilical endometriosis presents as a roundish tumuor that can either partly or completely occupy the umbilical scar with intermittent bleeding. Characteristically, the mass increases with the menstrual cycle, becoming more evident and usually harder and is associated with cyclic pain. Its pathogenesis remains uncertain. Clinical diagnosis is difficult, and umbilical endometriosis can be easily confused with other conditions such as benign and malignant tumours. Ultrasound examination is useful, and surgical excision is the treatment of choice. Several cases of malignant transformation have also been described. PMID- 19475891 TI - Thymoma arising in the wall of a thymic cyst. AB - A 54-year-old male, non smoker, began to suffer from persistent dyspnoea and fever. X-ray and CT scan showed a cystic lesion located in the left anterior mediastinum. This lesion was removed instead of the initially scheduled surgical resection with video-assisted thoracoscopic surgery (VATS) preceded by fine needle aspiration (FNA). A diagnosis of thymoma arising in the wall of thymic cyst was made. Such a rare tumour should be taken into consideration in treating patients with a cystic mediastinal lesion, before VATS and FNA. PMID- 19475892 TI - Undifferentiated pleomorphic sarcoma of the broad ligament. AB - AIMS: Sarcomas of the broad ligament are exceptionally rare. To our knowledge, the present case is the first description of undifferentiated pleomorphic sarcoma (UPS) occurring in the broad ligament. Herein, we report this unusual case, and discuss differential diagnoses and treatment. RESULTS: A 55-year-old postmenopausal woman was admitted for lower abdominal pain and vaginal spotting. Radiological examination revealed a latero-uterine mass that was independent of the surrounding organs. Treatment consisted in a total resection of the mass in addition to total abdominal hysterectomy and bilateral salpingo-oophorectomy. Based on histological examination, immunohistochemical study and quantitative PCR, a diagnosis of undifferentiated pleomorphic sarcoma (UPS) was made. The patient was lost to follow-up for 6 months, and then presented with a local recurrence of the tumour in addition to secondary pulmonary and vertebral localizations. The patient died less than one year after the first diagnosis. CONCLUSIONS: Diagnosis of UPS of the broad ligament is based on exclusion using a large panel of antibodies. There is no consensus for treatment. The prognosis of this disease cannot be assessed due to its rarity, but it can be hypothesized that early recurrence is indicative of poor prognosis. PMID- 19475893 TI - Primary high grade sarcoma of the specialised prostatic stroma: a case report with clinico-pathological considerations. AB - Malignant tumours of the prostate other than carcinomas are rare. One such malignant tumours arising from the specialised stromal tissue of the prostate is stromal prostatic sarcoma (namely low-grade and high-grade). Herein, we report the clinico-pathological features of a high grade stromal sarcoma of the prostate occurring in a 65-year-old man who presented for urinary obstructive symptoms. The clinical picture suggested a benign prostatic hyperplasia, and surgery consisting in a transcapsular adenomectomy was performed. Following a pathological diagnosis of high grade prostatic stromal sarcoma, a radical cystoprostatectomy and bilateral pelvic node dissection was performed showing residual high grade stromal sarcoma of the prostate and incidental in situ urothelial carcinoma of the bladder. No further medical treatments were planned. One year after surgery the patient is well with no evidence of local disease or distant metastases. PMID- 19475894 TI - Cystic mature teratoma and epidermoid cyst associated with granulosa cell tumour: a rare ovarian scenario. Two case reports and review of the literature. AB - We describe two cases of association between an ovarian granulosa cell tumour and a cystic mature teratoma and an epidermoid cyst. These are very rare combinations that might lead to incorrect diagnostic interpretation, since the simultaneous presence, on routine gross and microscopic examination, of a cystic squamous lesion, intimately connected with (case 1), or contralateral to (case 2) a solid, histologically trabecular or microfollicular tumour, might suggest a diagnosis of a carcinoid tumour in a mature cystic teratoma. The differential diagnostic problems and a review of the literature are presented. PMID- 19475895 TI - Paratesticular angiomyofibroblastoma: case report and review of the literature. AB - Angiomyofibroblastoma is a rare, benign, mesenchymal tumour occurring mainly in the female genital tract, and more rarely, in males. We present a new case of angiomyofibroblastoma arising in the left inguinal region of an 83-year-old man. The tumour was well circumscribed and measured 60 mm in maximum dimension. On microscopic examination, the tumour was composed of small spindle cells without atypia within a fibrous and myxoid stroma where scattered mononuclear inflammatory cells were found around the capillaries of the stroma. Immunohistochemical studies showed positive staining of tumour cells for vimentin, desmin, smooth muscle actin and CD34, and negative staining for PS100 and oestrogen and progesterone receptors. These histological findings are consistent with angiomyofibroblastoma. The patient was followed up for 4 years without recurrence. PMID- 19475896 TI - Glomus tumour of uncertain malignant potential. AB - A 71-year-old man presented with a several year story of a slowly enlarging, painful mass of the knee. Surgical findings showed a subcutaneous, well circumscribed mass fixed to the patella, and a wide resection was performed. Macroscopically, the tumour measured 6 x 5 x 5 cm and was well circumscribed. The tumour was characterised by superficial location, large size and focal marked atypia. In addition, areas of benign glomus tumour (GT) were identified. The findings appear to be consistent with the diagnosis of GT of uncertain malignant potential. PMID- 19475897 TI - Progress--but at what price? PMID- 19475898 TI - CARNA joins Facebook! PMID- 19475899 TI - Shades of humour. PMID- 19475900 TI - Voices from the class of 2012. Experiences in meeting clients for the first time. PMID- 19475901 TI - RNs break ground in Eden. PMID- 19475902 TI - Independent double-checks are vital, not perfect. PMID- 19475903 TI - NPs step up to improve patient access in Ontario. PMID- 19475904 TI - Trusts 'sidestepping' mandatory pay rises. PMID- 19475905 TI - The big issues in nursing. Interview by Steve Ford. PMID- 19475906 TI - Current standards of effective oral care provision are unacceptable. PMID- 19475907 TI - A rapid response intermediate care service for older people with mental health problems. AB - This article follows the development of an intermediate care service for older people with mental health needs and assesses the impact of the service on patients, carers and referrers, and the availability of dedicated elderly mentally ill (EMI) beds. PMID- 19475908 TI - Nasogastric tubes. 2: Risks and guidance on avoiding and dealing with complications. AB - This is the second of a two-part unit on nasogastric tube management. Part 1 explored the indications, patient preparation, insertion technique and methods of verifying correct intragastric position. This focuses on complications related to nasogastric tubes. PMID- 19475909 TI - Exploring NICE guidance on long-term sickness and incapacity for work. PMID- 19475910 TI - The importance of patients' oral health and nurses'role in assessing and maintaining it. AB - Oral hygiene is undervalued in terms of its effects on patient health and nutrition. Effective oral care reduces infection and promotes health. This article explores the evidence for appropriate assessment of oral health and provides guidance for effective oral care. PMID- 19475911 TI - An integrated approach to introducing and maintaining supervision: the 4S model. AB - Although strongly recommended as a matter of clinical governance for nurses and other health service professionals, supervision is not universally and robustly in place. This article outlines the 4S model--structure, skills, support and sustainability. This first puts in place a managerial structure, then teaches a solution-focused approach and skills to volunteer supervisors, as well as ensuring support and sustainability. PMID- 19475912 TI - On the experience of going 'back to the floor' for a day. PMID- 19475913 TI - 'Can the NMC support our care delivery ambitions'? PMID- 19475914 TI - Mercury cycling and bioaccumulation in a mine-dominated aquatic ecosystem: Clear Lake, California. PMID- 19475915 TI - The basis for ecotoxicological concern in aquatic ecosystems contaminated by historical mercury mining. AB - The Coast Range of California is one of five global regions that dominated historical production of mercury (Hg) until declining demand led to the economic collapse of the Hg-mining industry in the United States. Calcines, waste rock, and contaminated alluvium from inactive mine sites can release Hg (including methylmercury, MeHg) to the environment for decades to centuries after mining has ceased. Soils, water, and sediment near mines often contain high concentrations of total Hg (TotHg), and an understanding of the biogeochemical transformations, transport, and bioaccumulation of this toxic metal is needed to assess effects of these contaminated environments on humans and wildlife. We briefly review the environmental behavior and effects of Hg, providing a prelude to the subsequent papers in this Special Issue. Clear Lake is a northern California lake contaminated by wastes from the abandoned Sulphur Bank Mercury Mine, a U.S. Environmental Protection Agency Superfund Site. The primary toxicological problem with Hg in aquatic ecosystems is biotic exposure to MeHg, a highly toxic compound that readily bioaccumulates. Processes that affect the abundance of MeHg (including methylation and demethylation) strongly affect its concentration in all trophic levels of aquatic food webs. MeHg can biomagnify to high concentrations in aquatic food webs, and consumption of fish is the primary pathway for human exposure. Fish consumption advisories have been issued for many North American waters, including Clear Lake and other mine-impacted waters in California, as a means of decreasing MeHg exposure. Concerns about MeHg exposure in humans focus largely on developmental neurotoxicity to the fetus and children. Aquatic food webs are also an important pathway for MeHg exposure of wildlife, which can accumulate high, sometimes harmful, concentrations. In birds, wild mammals, and humans, MeHg readily passes to the developing egg, embryo, or fetus, life stages that are much more sensitive than the adult. The papers in this issue examine the origin, transport, transformations, bioaccumulation, and trophic transfer of Hg in Clear Lake, assess its potential effects on biota and humans, and provide information relevant to remediation of mine-impacted aquatic ecosystems. PMID- 19475916 TI - The legacy of mercury cycling from mining sources in an aquatic ecosystem: from ore to organism. AB - Clear Lake is the site of an abandoned mercury (Hg) mine (active intermittently from 1873 to 1957), now a U.S. Environmental Protection Agency Superfund Site. Mining activities, including bulldozing waste rock and tailings into the lake, resulted in approximately 100 Mg of Hg entering the lake's ecosystem. This series of papers represents the culmination of approximately 15 years of Hg-related studies on this ecosystem, following Hg from the ore body to the highest trophic levels. A series of physical, chemical, biological, and limnological studies elucidate how ongoing Hg loading to the lake is influenced by acid mine drainage and how wind-driven currents and baroclinic circulation patterns redistribute Hg throughout the lake. Methylmercury (MeHg) production in this system is controlled by both sulfate-reducing bacteria as well as newly identified iron-reducing bacteria. Sediment cores (dated with dichlorodiphenyldichlorethane [DDD], 210pb, and 14C) to approximately 250 cm depth (representing up to approximately 3000 years before present) elucidate a record of total Hg (TotHg) loading to the lake from natural sources and mining and demonstrate how MeHg remains stable at depth within the sediment column for decades to millenia. Core data also identify other stresses that have influenced the Clear Lake Basin especially over the past 150 years. Although Clear Lake is one of the most Hg-contaminated lakes in the world, biota do not exhibit MeHg concentrations as high as would be predicted based on the gross level of Hg loading. We compare Clear Lake's TotHg and MeHg concentrations with other sites worldwide and suggest several hypotheses to explain why this discrepancy exists. Based on our data, together with state and federal water and sediment quality criteria, we predict potential resulting environmental and human health effects and provide data that can assist remediation efforts. PMID- 19475918 TI - Use of tracers to quantify subsurface flow through a mining pit. AB - Three independent tracer experiments were conducted to quantify the through-flow of water from Herman Pit, an abandoned mercury (Hg) mine pit adjacent to Clear Lake, California, USA. The tracers used were Rhodamine-WT, sulfur hexafluoride, and a mixture of sulfur hexafluoride and neon-22. The tracers were injected into Herman Pit, a generally well-mixed water body of approximately 81,000 m2, and the concentrations were monitored in the mine pit, observation wells, and the lake for 2-3 months following each injection. The results for all three experiments showed that the tracer arrived at certain observation wells within days of injection. Comparing all the well data showed a highly heterogeneous response, with a small number of wells showing this near-instantaneous response and others taking months before the tracer was detectable. Tracer was also found in the lake on four occasions over a one-month period, too few to infer any pattern but sufficient to confirm the connection of the two water bodies. Using a simple mass balance model it was possible to determine the effective loss rate through advection for each of the tracers and with this to estimate the through-flow rate. The through-flow rate for all three experiments was approximately 630 L/s, at least 1-2 orders of magnitude larger than previous estimates, all of which had been based on geochemical inferences or other indirect measures of the pit through-flow. PMID- 19475917 TI - Pathways of acid mine drainage to Clear Lake: implications for mercury cycling. AB - Pore fluids from Clear Lake sediments collected near the abandoned Sulphur Bank Mercury Mine have low pH (locally <4) and elevated sulfate (> or =197 mmol/L), aluminum (> or =52 mmol/L), and iron (> or =28 mmol/L) contents derived from oxidation of sulfide minerals at the mine site. Acid mine drainage (AMD) is entering Clear Lake by advective subsurface flow nearest the mine and by diffusion at greater distances. Oxygen and hydrogen isotope ratios, combined with pore fluid compositions, constrain the sources and pathways of contaminated fluids. Sediment cores taken nearest the mine have the highest concentrations of dissolved sulfate, aluminum, and iron, which are contributed by direct subsurface flow of AMD from sulfide-bearing waste rock. Sediment cores as far as 100 m west of the Clear Lake shoreline show the presence of AMD that originated in the acidic lake that occupies the abandoned Herman Pit at the mine site. High sulfate content in the AMD has the potential to promote the activity of sulfate-reducing bacteria in the organic-rich lake sediments, which leads to methylation of Hg+2, making it both more toxic and bioavailable. Quantitative depletion of pore water sulfate at depth and sulfur isotope values of diagenetic pyrite near 0 per thousand indicate that sulfate availability limits the extent of sulfate reduction in the lake sediments away from the mine. Profiles of pore water sulfate in the sediments near the mine show that excess sulfate is available to support the activity of sulfate-reducing bacteria near the mine site. Enriched isotope values of dissolved sulfate (as high as 17.1 per thousand) and highly depleted isotope values for diagenetic pyrite (as low as -22.6 per thousand) indicate active bacterial sulfate reduction in the AMD-contaminated sediments. Sulfate- and iron-rich acid mine drainage entering Clear Lake by shallow subsurface flow likely needs to be controlled in order to lower the environmental impacts of Hg in the Clear Lake ecosystem. PMID- 19475919 TI - Mechanisms of contaminant transport in a multi-basin lake. AB - Tracer studies are combined with a three-dimensional (3-D) numerical modeling study to provide a robust description of hydrodynamic and particle transport in Clear Lake, a multi-basin, polymictic lake in northern California, USA. The focus is on the mechanisms of transport of contaminants away from the vicinity of the Sulphur Bank Mercury Mine and out of the Oaks Arm to the rest of the lake and the hydraulic connection existing among the sub-basins of the lake. Under stratified conditions, the rate of spreading of the tracer was found to be large. In less than a week the tracer spread from the eastern end of the Oaks Arm to the other basins. Under non-stratified conditions, the tracer spread more slowly and had a concentration that gradually diminished with distance from the injection location. The numerical results showed that the mechanisms accounting for these observed patterns occur in pulses, with maximum rates coinciding with the stratified periods. Stratification acts first to enhance the currents by inhibiting vertical momentum mixing and decoupling the surface currents from bottom friction. The diversity of the flow structures that results from the interaction of the wind and the density fields in the lake is responsible for the high dispersion rates. Contaminants originating in the Oaks Arm are shown to be transported into the Lower Arm following the surface currents and into the Upper Arm mainly through the bottom currents. It was also shown that, under stratified conditions, both the baroclinic (density driven) gradients and the wind forcing act jointly to exacerbate the interbasin exchange. PMID- 19475920 TI - Exchange flow in a shallow lake embayment. AB - Convectively driven currents can arise in the littoral zones of lakes, as a result of either differential heating or differential cooling of the shallow water. The result of these flows is to produce a surface flow away from shore with a bottom return flow or a bottom flow away from shore with a surface return flow. Measurements taken in a shallow embayment of Clear Lake, California, USA, show the presence of both kinds of convectively driven flows under a large variety of summer conditions. The magnitude of these flows is sufficient to transport material a distance on the order of 0.5 km during such events. Through both advection and dispersion the net result of this process would be to reduce the accumulation of particles and particle-associated contaminants such as mercury in the littoral zone and to move them offshore where they are more prone to permanent burial or further transport. PMID- 19475921 TI - Is Clear Lake methylmercury distribution decoupled from bulk mercury loading? AB - Clear Lake is the site of the abandoned Sulphur Bank Mercury Mine, active periodically from 1873 to 1957, resulting in approximately 100 Mg of mercury (Hg) being deposited into the lake's ecosystem. Concentrations of total (primarily inorganic) Hg (TotHg) in Clear Lake are some of the highest reported worldwide for sediments (up to 4.4 x 10(5) ng/g [ppb dry mass]) and water (up to 4 x 10(-1) microg/L [= ppb]). However, the ratio of methylmercury (MeHg) to TotHg at Clear Lake indicates that the methylation process is mostly decoupled from bulk inorganic Hg loading, with Hg in lower trophic level biota significantly less than anticipated compared with other Hg-contaminated sites worldwide. This may be due to several factors, including: (1) reduced bioavailability of Hg derived from the mine (i.e., cinnabar, metacinnabar, and corderoite), (2) the alkaline nature of the lake water, (3) the shallow depth of the lake, which prevents stratification and subsequent methylation in a stratified hypolimnion, and (4) possible dilution of MeHg by a highly productive system. However, while bulk inorganic Hg loading to the lake may not contribute significantly to the bioaccumulation of Hg, acid mine drainage (AMD) from the mine likely promotes Hg methylation by sulfate-reducing and iron-reducing bacteria, making AMD a vehicle for the production of highly bioavailable Hg. If Clear Lake were deeper, less productive, or less alkaline, biota would likely contain much more MeHg than they do presently. Comparisons of MeHg:TotHg ratios in sediments, water, and biota from sites worldwide suggest that the highest production of MeHg may be found at sites influenced by chloralkali plants, followed by sites influenced by gold and silver mines, with the lowest production of MeHg observed at cinnabar and metacinnabar Hg mines. These data also suggest that the total maximum daily load (TMDL) process for Hg at Clear Lake, as currently implemented to reduce contamination in fishes for the protection of wildlife and humans, may be flawed because the metric used to implement Hg load reduction (i.e., TotHg) is not directly proportional to the critical form of Hg that is being bioaccumulated (i.e., MeHg). PMID- 19475922 TI - Mercury in abiotic matrices of Clear Lake, California: human health and ecotoxicological implications. AB - Mercury (Hg) from Hg mining at Clear Lake, California, USA, has contaminated water and sediments for over 130 years and has the potential to affect human and environmental health. With total mercury (TotHg) concentrations up to 438 mg/kg (dry mass) in surficial sediments and up to 399 ng/L in lake water, Clear Lake is one of the most Hg-contaminated lakes worldwide. Particulate Hg in surface water near the mine ranges from 10,000 to 64,000 ng/g; TotHg declines exponentially with distance from the Sulphur Bank Mercury Mine. From 1992 to 1998, no significant long-term trends for TotHg or methylmercury (MeHg) in sediments or water were observed, but peaks of both TotHg and MeHg occurred following a 1995 flooding event. Sediments and water exhibit summer/fall maxima and winter/spring minima for MeHg, but not TotHg. Sediment TotHg has not declined significantly a decade after remediation in 1992. At the mine site, aqueous TotHg reached 374,000 ng/L in unfiltered groundwater. Pore water sulfate in sediments varies seasonally from 112 mg/L in summer/fall (when Hg methylation is highest) to 3300 mg/L in winter. While TotHg is exceptionally high in both sediments and water, MeHg is substantially lower than would be expected based on the bulk Hg loading to the lake and in comparison with other sites worldwide. Total mercury in Clear Lake water does not exceed the Safe Drinking Water Act criteria, but it sometimes greatly exceeds human health criteria established by the Great Lakes Initiative, U.S. Environmental Protection Agency water quality guidelines, and the California Toxics Rule criterion. Methylmercury concentrations exceed the Great Lakes Initiative criterion for MeHg in water at some sites only during summer/fall. Relative to ecological health, Clear Lake sediments greatly exceed the National Oceanic and Atmospheric Administration's benthic fauna Sediment Quality Guidelines for toxic effects, as well as the more concensus-based Threshold Effects Concentration criteria. Based on these criteria, Hg-contaminated sediments and water from Clear Lake are predicted to have some lethal and sublethal effects on specific resident aquatic species. However, based on unique physical and chemical characteristics of the Clear Lake environment, MeHg toxicity may be significantly less than anticipated from the large inorganic Hg loading. PMID- 19475923 TI - Mine-derived mercury: effects on lower trophic species in Clear Lake, California. AB - Considerable ecological research on mercury (Hg) has focused on higher trophic level species (e.g., fishes and birds), but less on lower trophic species. Clear Lake, site of the abandoned Sulphur Bank Mercury Mine, provides a unique opportunity to study a system influenced by mine-derived Hg. An exponentially decreasing gradient of total Hg (TotHg) away from the mine allowed us to evaluate Hg bioaccumulation in planktonic and benthic invertebrates and evaluate population- and community-level parameters that might be influenced by Hg. Studies from 1992-1998 demonstrated that TotHg in lower trophic species typically decreased exponentially away from the mine, similar to trends observed in water and sediments. However, a significant amount of invertebrate TotHg (approximately 60% for sediment-dwelling chironomid insect larvae) likely derives from Hg-laden particles in their guts. Spatially, whole-body methylmercury (MeHg) did not typically exhibit a significant decrease with increasing distance from the mine. Temporally, TotHg concentrations in plankton and chironomids did not exhibit any short-term (seasonal or annual) or long-term (multiyear) trends. Methylmercury, however, was elevated during late summer/fall in both plankton and chironomids, but it exhibited no long-term increase or decrease during this study. Although data from a 50-yr monitoring program for benthic chaoborid and chironomid larvae documented significant population fluctuations, they did not demonstrate population-level trends with respect to Hg concentrations. Littoral invertebrates also exhibited no detectable population- or community-level trends associated with the steep Hg gradient. Although sediment TotHg concentrations (1-1200 mg/kg dry mass) exceed sediment quality guidelines by up to 7000 times, it is notable that no population- or community-level effects were detected for benthic and planktonic taxa. In comparison with other sites worldwide, Clear Lake's lower trophic species typically have significantly higher TotHg concentrations, but comparable or lower MeHg concentrations, which may be responsible for the discrepancy between highly elevated TotHg concentrations and the general lack of observed population- or community-level effects. These data suggest that MeHg, as well as TotHg, should be used when establishing sediment quality guidelines. In addition, site-specific criteria should be established using the observed relationship between MeHg and observed ecological responses. PMID- 19475924 TI - Spatiotemporal trends in fish mercury from a mine-dominated ecosystem: Clear Lake, California. AB - Clear Lake, California, USA, receives acid mine drainage and mercury (Hg) from the Sulphur Bank Mercury Mine, a U.S. Environmental Protection Agency (U.S. EPA) Superfund Site that was active intermittently from 1873 to 1957 and partially remediated in 1992. Mercury concentrations were analyzed primarily in four species of Clear Lake fishes: inland silversides (Menidia beryllina, planktivore), common carp (Cyprinus carpio, benthic scavenger/omnivore), channel catfish (Ictalurus punctatus, benthic omnivorous predator), and largemouth bass (Micropterus salmoides, piscivorous top predator). These data represent one of the largest fish Hg data sets for a single site, especially in California. Spatially, total Hg (TotHg) in silversides and bass declined with distance from the mine, indicating that the mine site represents a point source for Hg loading to Clear Lake. Temporally, fish Hg has not declined significantly over 12 years since mine site remediation. Mercury concentrations were variable throughout the study period, with no monotonic trends of increase or decrease, except those correlated with boom and bust cycles of an introduced fish, threadfin shad (Dorosoma petenense). However, stochastic events such as storms also influence juvenile largemouth bass Hg as evidenced during an acid mine drainage overflow event in 1995. Compared to other sites regionally and nationally, most fish in Clear Lake exhibit Hg concentrations similar to other Hg-contaminated sites, up to approximately 2.0 mg/kg wet mass (WM) TotHg in largemouth bass. However, even these elevated concentrations are less than would be anticipated from such high inorganic Hg loading to the lake. Mercury in some Clear Lake largemouth bass exceeded all human health fish consumption guidelines established over the past 25 years by the U.S. Food and Drug Administration (1.0 mg/kg WM), the National Academy of Sciences (0.5 mg/kg WM), and the U.S. EPA (0.3 mg/kg WM). Mercury in higher trophic level fishes exceeds ecotoxicological risk assessment estimates for concentrations that would be safe for wildlife, specifically the nonlisted Common Merganser and the recently delisted Bald Eagle. Fish populations of 11 out of 18 species surveyed exhibited a significant decrease in abundance with increasing proximity to the mine; this decrease is correlated with increasing water and sediment Hg. These trends may be related to Hg or other lake-wide gradients such as distribution of submerged aquatic vegetation. PMID- 19475925 TI - Mercury trophic transfer in a eutrophic lake: the importance of habitat-specific foraging. AB - Mercury (Hg) trophic transfer and bioaccumulation in fish from a mine-impacted, eutrophic lake were examined in relation to foraging habitat, trophic position, and size. Diet analysis indicated that there were clear ontogenetic shifts in foraging habitats and trophic position. Pelagic diet decreased and benthic diet increased with increasing fish length in bluegill, black crappie, inland silverside, and largemouth bass, whereas there was no shift for prickly sculpin or threadfin shad. Stable carbon isotope values (delta13C) were inversely related to the proportion of pelagic prey items in the diet, but there was no clear relationship with benthic foraging. There were distinct differences between pelagic and benthic prey basal delta13C values, with a range of approximately -28 per thousand in pelagic zooplankton to approximately -20 per thousand in benthic caddisflies. Profundal prey such as chironomid larvae had intermediate delta13C values of approximately -24 per thousand, reflecting the influence of pelagic detrital subsidies and suppressing the propagation of the benthic carbon isotope signal up the food chain. Fish total mercury (TotHg) concentrations varied with habitat-specific foraging, trophic position, and size; however, the relationships differed among species and ages. When controlling for the effects of species, length, and trophic position, TotHg and delta13C were positively correlated, indicating that Hg trophic transfer is linked to benthic foraging. When examined on a species-specific basis, TotHg was positively correlated with delta13C only for bluegill, largemouth bass, and threadfin shad. However, diet-based multiple regression analyses suggested that TotHg also increased with benthic foraging for inland silverside and black crappie. In both species, benthic prey items were dominated by chironomid larvae, explaining the discrepancy with delta13C. These results illustrate the importance of foraging habitat to Hg bioaccumulation and indicate that pelagic carbon can strongly subsidize the basal energy sources of benthic organisms. PMID- 19475926 TI - Changes in fish diets and food web mercury bioaccumulation induced by an invasive planktivorous fish. AB - The invasion, boom, collapse, and reestablishment of a population of the planktivorous threadfin shad in Clear Lake, California, USA, were documented over a 20-year period, as were the effects of changing shad populations on diet and mercury (Hg) bioaccumulation in nearshore fishes. Threadfin shad competitively displaced other planktivorous fish in the lake, such as inland silversides, young of-year (YOY) largemouth bass, and YOY bluegill, by reducing zooplankton abundance. As a result, all three species shifted from a diet that was dominated by zooplankton to one that was almost entirely zoobenthos. Stable carbon isotopes corroborated this pattern with each species becoming enriched in delta13C, which is elevated in benthic vs. pelagic organisms. Concomitant with these changes, Hg concentrations increased by approximately 50% in all three species. In contrast, obligate benthivores such as prickly sculpin showed no relationship between diet or delta13C and the presence of threadfin shad, suggesting that effects of the shad were not strongly linked to the benthic fish community. There were also no changes in Hg concentrations of prickly sculpin. The temporary extirpation of threadfin shad from the lake resulted in zooplankton densities, foraging patterns, isotope ratios, and Hg concentrations in pelagic fishes returning to pre-shad values. These results indicate that even transient perturbations of the structure of freshwater food webs can result in significant alterations in the bioaccumulation of Hg and that food webs in lakes can be highly resilient. PMID- 19475927 TI - Mercury residues and productivity in osprey and grebes from a mine-dominated ecosystem. AB - Mercury (Hg) and reproduction and status of Western and Clark's Grebes (Aechmophorus sp.) and Osprey (Pandion haliaetus) were studied from 1992 through 2001 and then less intensely through 2006 at Clear Lake, California, USA. Remediation to reduce Hg loading from the Sulphur Bank Mercury Mine was initiated in 1992. Mercury in grebe feathers declined monotonically from approximately 23 mg/kg dry mass (DM) in 1967-1969 to 1 mg/kg in 2003, but then increased to 7 mg/kg in 2004-2006. Mercury in Osprey feathers varied similarly, with mean values of 20 mg/kg DM in 1992, declining to a low of 2 mg/kg in 1998, but increasing to 23 mg/kg in 2003, and 12 mg/kg in 2006. Mercury in Osprey feathers at our reference site (Eagle Lake, California) remained low (1-8 ppm) throughout the entire period, 1992-2003. Grebe productivity at Clear Lake improved from approximately 0.1 to 0.5 fledged young per adult during the latter part of the study when human disturbance was prevented. At that period in time, improved productivity did not differ from our reference site at Eagle Lake. Human disturbance, however, as a co-factor made it impossible to evaluate statistically subtle Hg effects on grebe productivity at Clear Lake. Osprey reproduced sufficiently to maintain increasing breeding numbers from 1992 to 2006. Mercury in Clear Lake water, sediments, invertebrates, and fish did not decline from 1992 to 2003, but a shift in trophic structure induced by an introduced planktivorous fish species may have caused significant alterations in Hg concentrations in several species of prey fishes that may have produced concomitant changes in Osprey and grebe Hg exposure. The temporary declines observed in grebe and Osprey feather residues in the late 1990s, with coincidental improvements in reproductive performance, however, could not be attributed to remediation at the mine site. PMID- 19475928 TI - Clear Lake sediments: anthropogenic changes in physical sedimentology and magnetic response. AB - We analyzed the sedimentological characteristics and magnetic properties of cores from the three basins of Clear Lake, California, USA, to assess the depositional response to a series of land use changes that occurred in the watershed over the 20th century. Results indicate that distinct and abrupt shifts in particle size, magnetic concentration/mineralogy, and redox conditions occur concurrently with a variety of ecological and chemical changes in lake bed sediments. This coincidence of events occurred around 1927, a datum determined by an abrupt increase in total mercury (Hg) in Clear Lake cores and the known initiation of open-pit Hg mining at the Sulphur Bank Mercury Mine, confirmed by 210Pb dating. Ages below the 1927 horizon were determined by accelerator mass spectrometry on 14C of coarse organic debris. Calculated sedimentation rates below the 1927 datum are approximately 1 mm/yr, whereas rates from 1927 to 2000 are up to an order of magnitude higher, with averages of approximately 3.5-19 mm/yr. In both the Oaks and Upper Arms, the post-1927 co-occurrence of abrupt shifts in magnetic signatures with color differences indicative of changing redox conditions is interpreted to reflect a more oxygenated diagenetic regime and rapid burial of sediment below the depth of sulfate diffusion. Post-1927 in the Oaks Arm, grain size exhibits a gradual coarsening-upward pattern that we attribute to the input of mechanically deposited waste rock related to open-pit mining activities at the mine. In contrast, grain size in the Upper Arm exhibits a gradational fining upward after 1927 that we interpret as human-induced erosion of fine-grained soils and chemically weathered rocks of the Franciscan Assemblage by heavy earthmoving equipment associated with a road- and home-building boom, exacerbated by stream channel mining and wetlands destruction. The flux of fine-grained sediment into the Upper Arm increased the nutrient load to the lake, and that in turn catalyzed profuse cyanobacterial blooms through the 20th century. The resulting organic biomass, in combination with the increased inorganic sediment supply, contributed to the abrupt increase in sedimentation rate after 1927. PMID- 19475929 TI - Anthropogenic stressors and changes in the Clear Lake ecosystem as recorded in sediment cores. AB - Sediment cores were collected to investigate multiple stresses on Clear Lake, California, USA, through the period of European occupation to the present day. Earlier workers suggested the hypothesis that the use of mechanized earthmoving equipment, starting in the 1920s and 1930s, was responsible for erosion, mercury (Hg) contamination, and habitat loss stresses. Cores (approximately 2.5 m in depth) were collected in 1996 and 2000 from each of the three arms of the lake. Carbon-14 dating suggests that these cores represent as much as 3000 years of the lake's history, beginning long before European settlement. Total mercury (TotHg) and methylmercury (MeHg), dry matter, water, carbon, nitrogen, phosphorus, sulfur, and the stable isotopes 13C and 15N were measured at 5-cm intervals. Nearly all parameters show major changes at depths of 58-135 cm, beginning at ca. 1927 (dated with 210Pb). Accepting this date for concomitant major changes in seven cores yields an estimated 8.6 mm/yr average sedimentation rate after 1927. Pre-1927 sedimentation rates were approximately 1 mm/yr. Total mercury and MeHg, dry matter, phosphorus, and 15N increase significantly, whereas nitrogen, sulfur, carbon, and water content decrease significantly above the 1927 horizon. Both TotHg and MeHg show extremely large increases (roughly 10-fold) above the 1927 horizon. A peak in inorganic deposition rate and minimum values for percentage of water is present at depths corresponding to ca. 1970. Interestingly, the first 75 years of European settlement in the Clear Lake basin (including the most productive years of the Sulphur Bank Mercury Mine) appeared to have had undetectable effects on lake cores. Changes since 1927 were dramatic. The large increase in Hg beginning about 1927 corresponds to the use of heavy equipment to exploit the ore deposit at the mine using open-pit methods. Increases in sediment deposition from increased earthmoving in the basin and sulfate loading from the mine are the most likely explanations for the dramatic changes seen in the post 1927 sections of the cores. PMID- 19475930 TI - Vertical stability of mercury in historic and prehistoric sediments from Clear Lake, California. AB - Clear Lake, California, USA, is the site of the Sulphur Bank Mercury Mine, now a U.S. Environmental Protection Agency Superfund Site. Intermittent mining from 1873 to 1957 resulted in approximately 100 Mg of mercury (Hg) being deposited into the lake's ecosystem. Sediment cores to approximately 2.5 m depth (dated using 210Pb and 14C) represent approximately 3000 years of sedimentation. Clear Lake sediments have experienced Hg deposition from anthropogenic sources (mining) during historic times (to the mid-1900s) and geologic sources during prehistoric times (prior to the mid-1800s). This provides a unique opportunity to evaluate hypotheses relating to (1) the influence of the mine on Hg loading to the lake and (2) the potential upward mobilization of Hg by diagenetic processes proposed by some as an alternative explanation for increased Hg concentrations at the surface of the sediment column believed to be caused by increased global atmospheric deposition. Although Hg mining began in 1873, no significant evidence of anthropogenic Hg loading was detected in cores prior to open-pit mining ca. 1927, which also involved bulldozing mine waste rock and tailings into the lake. Exponential increases in total Hg (TotHg) and methylmercury (MeHg) were observed above the 1927 horizon, where estimated sedimentation rates were 2.2-20.4 mm/yr and peaks of both forms of Hg maintained vertical stability within the sediment column. Below the 1927 horizon, a slow increase in both TotHg and MeHg with depth was observed from approximately 1000 to 3000 years before present, where sedimentation rates ranged from approximately 0.6 to 2.0 mm/yr and elevated Hg profiles appear stable. Vertical stability of Hg in the shallow and deep sediment column suggests that both TotHg and MeHg do not undergo diagenetic upward mobilization within the sediment column under rapid or slow sedimentation rates. Because (1) these data were collected at a site with known anthropogenic and geologic sources and (2) regions of elevated Hg concentrations from both sources remain stable within the sediment column under very different sedimentation regimes, these results also support the hypothesis that elevated Hg at the surface of cores in other worldwide locations likely represents global atmospheric deposition rather than upward diagenetic mobilization. PMID- 19475931 TI - Outlook hazy for climate regulations? PMID- 19475932 TI - After the clean air mercury rule: prospects for reducing mercury emissions from coal-fired power plants. AB - Recent court decisions have affected the EPA's regulation of mercury emissions from coal burning, but some state laws are helping to clear the air. PMID- 19475933 TI - Environmental comparison of biosolids management systems using life cycle assessment. AB - To fill a gap in the information available to nonmetropolitan policy makers, eight scenarios combining processing technologies and end-uses for biosolids products associated with a 40,000 equivalent-person town were modeled using environmental life cycle assessment (LCA). An uncertainty analysis examined several key assumptions. The results showed that the reuse of biosolids products can be environmentally beneficial but transportation distances can change the preferences between technologies, and drying biosolids using petrochemical methane rather than biogas (produced endogenously in the wastewater facility) significantly worsens environmental performance. System scale can also invert option preferences. This work demonstrates an application of LCA to a strategic engineering question. We also examine the methodological feasibility of considering carbon sequestration and water offsets beyond those typical of previous studies. As the development of scientific data regarding the benefits of biosolids recycling develops,there may be potentialto reward agricultural businesses that choose to reduce their environmental burdens using biosolids. A life cycle management approach to this will be necessary. PMID- 19475934 TI - Energy and air emission effects of water supply. AB - Life-cycle air emission effects of supplying water are explored using a hybrid life-cycle assessment For the typically sized U.S. utility analyzed, recycled water is preferable to desalination and comparable to importation. Seawater desalination has an energy and air emission footprint that is 1.5-2.4 times larger than that of imported water. However, some desalination modes fare better; brackish groundwater is 53-66% as environmentally intensive as seawater desalination. The annual water needs (326 m3) of a typical Californian that is met with imported water requires 5.8 GJ of energy and creates 360 kg of CO2 equivalent emissions. With seawater desalination, energy use would increase to 14 GJ and 800 kg of CO2 equivalent emissions. Meeting the water demand of California with desalination would consume 52% of the state's electricity. Supply options were reassessed using alternative electricity mixes, including the average mix of the United States and several renewable sources. Desalination using solar thermal energy has lower greenhouse gas emissions than that of imported and recycled water (using California's electricity mix), but using the U.S. mix increases the environmental footprint by 1.5 times. A comparison with a more energy-intensive international scenario shows that CO2 equivalent emissions for desalination in Dubai are 1.6 times larger than in California. The methods, decision support tool (WEST), and results of this study should persuade decision makers to make informed water policy choices by including energy consumption and material use effects in the decision-making process. PMID- 19475935 TI - Water embodied in bioethanol in the United States. AB - Prior studies have estimated that a liter of bioethanol requires 263-784 L of water from corn farm to fuel pump, but these estimates have failed to account for the widely varied regional irrigation practices. By using regional time-series agricultural and ethanol production data in the U.S., this paper estimates the state-level field-to-pump water requirement of bioethanol across the nation. The results indicate that bioethanol's water requirements can range from 5 to 2138 L per liter of ethanol depending on regional irrigation practices. The results also show that as the ethanol industry expands to areas that apply more irrigated water than others, consumptive water appropriation by bioethanol in the U.S. has increased 246% from 1.9 to 6.1 trillion liters between 2005 and 2008, whereas U.S. bioethanol production has increased only 133% from 15 to 34 billion liters during the same period. The results highlight the need to take regional specifics into account when implementing biofuel mandates. PMID- 19475936 TI - Concentrations and emissions of polybrominated diphenyl ethers from U.S. houses and garages. AB - Concentrations of polybrominated diphenyl ethers (PBDEs) and other brominated flame retardants (BFRs) have been rapidly increasing in fish, birds, sediments, indoor environments, and humans, but emission sources and exposure pathways of these pollutants remain poorly understood. The many BFR-containing materials in buildings constitute a large reservoir of these compounds, and in-use releases from this reservoir may be a significant environmental source. To estimate in-use releases from building materials and contents in residences, we monitored 12 houses and garages in two seasons and combined measurements of BFRs in air and settled dust, air exchange rates, and other information in an approach that utilized the building as a "natural" test chamber. Results were scaled to provide a first estimate of aggregate emission rates from U.S. houses. PBDE releases total about 4 microg h(-1) per house or 20 ng m(-2) h(-1), and U.S. houses and garages collectively release about 4100 kg y(-1). Most of these releases are settled floor dust, but about 20% are released directly to the ambient environment via airborne vapor and particulate matter. These screening-level estimates are subject to considerable uncertainty, but they have an advantage in that they reflect real-world conditions based on mass balance calculations. PMID- 19475937 TI - Delineation of multiple chlorinated ethene sources in an industrialized area--a forensic field study using compound-specific isotope analysis. AB - Identification of polluters and the allocation of contaminant sources are key tasks when evaluating complex subsurface contamination with multiple and overlapping plumes, as frequently found in industrial areas. Under certain conditions, compound-specific stable isotope analysis (CSIA) may provide decisive information in such environmental litigation studies. Here, we present an illustrative case study highlighting the potential and limitations of using delta13C values of halogenated hydrocarbons (tetrachloroethene and its transformation products) as a keytracer for discriminating different contaminant sources, even in the presence of biodegradation and a complex hydrogeology. A multiple-line-of-evidence approach, including evaluation of historical, hydrological, geochemical, and isotopic data as well as statistical analysis, was applied to unravel the contamination scenario at the site. A key factor was the coverage of a wide area of the contaminant plumes with highly precise delta13C values of chlorinated ethenes in groundwater at trace concentrations in the low microgram per liter range made possible by the application of online purge-and trap-GC/IRMS. Our work is the first successful example of a forensic isotope field study on chlorinated ethenes in a fractured bedrock aquifer. PMID- 19475938 TI - Composition and biodegradation of a synthetic oil spilled on the perennial ice cover of Lake Fryxell, Antarctica. AB - A helicopter crashed in January 2003 on the 5 m-thick perennial ice cover of Lake Fryxell, spilling synthetic turbine oil Aeroshell 500. Molecular compositions of the oils were analyzed by gas chromatography-mass spectrometry and compared to the composition of contaminants in ice, meltwater, and sediments collected a year after the accident. Aeroshell 500 is based on C20-C33 Pentaerythritol triesters (PET) with C5-C10 fatty acids susbstituents and contain a number of antioxidant additives, such as tricresyl phosphates. Biodegradation of this oil in the ice cover occurs when sediments are present PETs with short fatty acids substituents are preferentially degraded, whereas long chain fatty acids seem to hinder esters from hydrolysis by esterase derived from the microbial assemblage. It remains to be seen if the microbial ecosystem can degrade tricresyl phosphates. These more recalcitrant PET species and tricresyl phosphates are likely to persist and comprise the contaminants that may eventually cross the ice cover to reach the pristine lake water. PMID- 19475939 TI - Spatial pattern of groundwater arsenic occurrence and association with bedrock geology in greater Augusta, Maine. AB - In New England, groundwater arsenic occurrence has been linked to bedrock geology on regional scales. To ascertain and quantify this linkage at intermediate (10(0) 10(1) km) scales, 790 groundwater samples from fractured bedrock aquifers in the greater Augusta, Maine area are analyzed, and 31% of the sampled wells have arsenic concentrations >10 microg/L. The probability of [As] exceeding 10 microg/L mapped by indicator kriging is highest in Silurian pelite-sandstone and pelite-limestone units (approximately 40%). This probability differs significantly (p < 0.001) from those in the Silurian-Ordovician sandstone (24%),the Devonian granite (15%), and the Ordovician-Cambrian volcanic rocks (9%). The spatial pattern of groundwater arsenic distribution resembles the bedrock map. Thus, bedrock geology is associated with arsenic occurrence in fractured bedrock aquifers of the study area at intermediate scales relevant to water resources planning. The arsenic exceedance rate for each rock unit is considered robust because low, medium, and high arsenic occurrences in four cluster areas (3-20 km2) with a low sampling density of 1-6 wells per km2 are comparable to those with a greater density of 5-42 wells per km2. About 12,000 people (21% of the population) in the greater Augusta area (approximately 1135 km2) are at risk of exposure to >10 microg/L arsenic in groundwater. PMID- 19475940 TI - Mercury cycling in stream ecosystems. 1. Water column chemistry and transport. AB - We studied total mercury (THg) and methylmercury (MeHg) in eight streams, located in Oregon, Wisconsin, and Florida, that span large ranges in climate, landscape characteristics, atmospheric Hg deposition, and water chemistry. While atmospheric deposition was the source of Hg at each site, basin characteristics appeared to mediate this source by providing controls on methylation and fluvial THg and MeHg transport. Instantaneous concentrations of filtered total mercury (FTHg) and filtered methylmercury (FMeHg) exhibited strong positive correlations with both dissolved organic carbon (DOC) concentrations and streamflow for most streams, whereas mean FTHg and FMeHg concentrations were correlated with wetland density of the basins. For all streams combined, whole water concentrations (sum of filtered and particulate forms) of THg and MeHg correlated strongly with DOC and suspended sediment concentrations in the water column. PMID- 19475941 TI - Mercury cycling in stream ecosystems. 2. Benthic methylmercury production and bed sediment-pore water partitioning. AB - Mercury speciation, controls on methylmercury (MeHg) production, and bed sediment pore water partitioning of total Hg (THg) and MeHg were examined in bed sediment from eight geochemically diverse streams where atmospheric deposition was the predominant Hg input. Across all streams, sediment THg concentrations were best described as a combined function of sediment percent fines (%fines; particles < 63 microm) and organic content. MeHg concentrations were best described as a combined function of organic content and the activity of the Hg(II)-methylating microbial community and were comparable to MeHg concentrations in streams with Hg inputs from industrial and mining sources. Whole sediment tin-reducible inorganic reactive Hg (Hg(II)R) was used as a proxy measure for the Hg(II) pool available for microbial methylation. In conjunction with radiotracer-derived rate constants of 203Hg(II) methylation, Hg(II)R was used to calculate MeHg production potential rates and to explain the spatial variability in MeHg concentration. The %Hg(II)R (of THg) was low (2.1 +/- 5.7%) and was inversely related to both microbial sulfate reduction rates and sediment total reduced sulfur concentration. While sediment THg concentrations were higher in urban streams, %MeHg and %Hg(II)R were higher in nonurban streams. Sediment pore water distribution coefficients (log Kd's) for both THg and MeHg were inversely related to the log-transformed ratio of pore water dissolved organic carbon (DOC) to bed sediment %fines. The stream with the highest drainage basin wetland density also had the highest pore water DOC concentration and the lowest log Kd's for both THg and MeHg. No significant relationship existed between overlying water MeHg concentrations and those in bed sediment or pore water, suggesting upstream sources of MeHg production may be more important than local streambed production as a driver of water column MeHg concentration in drainage basins that receive Hg inputs primarily from atmospheric sources. PMID- 19475942 TI - Mercury cycling in stream ecosystems. 3. Trophic dynamics and methylmercury bioaccumulation. AB - Trophic dynamics (community composition and feeding relationships) have been identified as important drivers of methylmercury (MeHg) bioaccumulation in lakes, reservoirs, and marine ecosystems. The relative importance of trophic dynamics and geochemical controls on MeHg bioaccumulation in streams, however, remains poorly characterized. MeHg bioaccumulation was evaluated in eight stream ecosystems across the United States (Oregon, Wisconsin, and Florida) spanning large ranges in climate, landscape characteristics, atmospheric Hg deposition, and stream chemistry. Across all geographic regions and all streams, concentrations of total Hg (THg) in top predator fish and forage fish, and MeHg in invertebrates, were strongly positively correlated to concentrations of filtered THg (FTHg), filtered MeHg (FMeHg), and dissolved organic carbon (DOC); to DOC complexity (as measured by specific ultraviolet absorbance); and to percent wetland in the stream basins. Correlations were strongest for nonurban streams. Although regressions of log[Hg] versus delta15N indicate that Hg in biota increased significantly with increasing trophic position within seven of eight individual streams, Hg concentrations in top predator fish (including cutthroat, rainbow, and brown trout; green sunfish; and largemouth bass) were not strongly influenced by differences in relative trophic position. Slopes of log[Hg] versus delta15N, an indicator of the efficiency of trophic enrichment, ranged from 0.14 to 0.27 for all streams. These data suggest that, across the large ranges in FTHg (0.14-14.2 ng L(-1)), FMeHg (0.023-1.03 ng L(-1)), and DOC (0.50-61.0 mg L(-1)) found in this study, Hg contamination in top predatorfish in streams likely is dominated by the amount of MeHg available for uptake at the base of the food web rather than by differences in the trophic position of top predator fish. PMID- 19475943 TI - Sorption of polycyclic aromatic hydrocarbons to carbohydrates and lipids of ryegrass root and implications for a sorption prediction model. AB - Plant lipids were considered as the main storage sites for hydrophobic organic contaminants while carbohydrates were generally underestimated, and the lipid water partition coefficients (Klip) of contaminants were assumed to be the same as the corresponding octanol-water partition coefficients (Kow). Sorption of five polycyclic aromatic hydrocarbons (PAHs) to ryegrass root and its carbohydrates and lipids was investigated to evaluate the role of carbohydrates and lipids on sorption of organic contaminants to plant Results revealed that sorption of PAHs to ryegrass root was actually regulated by both carbohydrates and lipids rather than lipids individually, as generally assumed. Kch (carbohydrates-water partition coefficient) and Klip could be estimated with the corresponding Kow values: log Kch = 1.23 log Kow - 2.42 and log Klip = 1.23 log Kow - 0.78. Although the affinity of PAHs for lipids appears to be about 1.64 orders of magnitudes higher than that for carbohydrates, sorption of PAHs to carbohydrates could not be neglected because of its predominant weight fraction in plants (about 98 times of lipids for ryegrass root). An improved model containing integral roles of carbohydrates and lipids was established, which showed excellent accuracy for predicting the sorption of organic contaminants to plants. PMID- 19475944 TI - Empirical investigation of the Junge variability-lifetime relationship using long term monitoring data on polychlorinated biphenyl concentrations in air. AB - In 1974, Junge derived an empirical relationship between the variability of concentrations of volatile trace gases in air at remote locations and their atmospheric residence time. Here, the Junge relationship is adapted to incorporate the deposition and revolatilization of semivolatile chemicals and applied to interpret nearly a decade of data on polychlorinated biphenyl (PCB) concentrations in air. A multimedia fate model, which accounts for deposition and revolatilization, is used to estimate the characteristic travel distance (CTD) for PCBs, where CTD serves as a measure of the effective atmospheric lifetime for semivolatile organic chemicals. Data are taken from sites of the Integrated Atmospheric Deposition Network in the North American Great Lakes and the Alert monitoring station in the Arctic, which is operated by the Canadian Northern Contaminants Program. Five factors that may introduce variability into measured concentrations are defined. By suppressing the effect of three of these factors in the data analysis, we identified variability consistent with the Junge relationship in many of the annual data sets (62%), with the relationship showing statistical significance (p < 0.05) in 23% of these annual data sets. The more remote monitoring sites from the Great Lakes region display the highest number of statistically significant Junge-type relationships between the variability in concentrations in air and estimated long-range transport potential in air. At sites in close proximity to areas of high population density, variability in PCB concentrations in air displays patterns that are consistent with primary or secondary temperature-driven volatilization sources. Analysis of variability in long-term monitoring data, using the techniques developed and illustrated here, provides useful insights into the factors that control the behavior of persistent semivolatile chemicals in the environment. PMID- 19475945 TI - Measurement of atmospheric hydroxyacetone, glycolaldehyde, and formaldehyde. AB - A method has been modified and optimized for the measurements of hydroxyacetone as well as formaldehyde and glycolaldehyde, based on aqueous scrubbing using a coil sampler followed by DNPH derivatization and HPLC analysis. Derivatization equilibrium and kinetics were studied to optimize the hydroxyacetone-DNPH derivative yield. It was found that the low sensitivity of hydroxyacetone by this method is due to a relatively small equilibrium constant for the hydroxyacetone DNPH derivatization reaction, and thus it can be improved by increasing DNPH reagent concentration. In a medium containing 500 microM DNPH and 50 mM HCl, the derivatization reaches equilibrium within 30 min. An online reagent purification procedure using a DNPH-saturated Sep-Pak C-18 cartridge effectively removed hydrazone impurities in the DNPH reagent solution, and a sample preconcentration procedure using a C-18 guard column greatly enhanced the sensitivity and lowered the detection limits. The lower detection limits of the system under optimized conditions are 30, 9, and 36 pptv for hydroxyacetone, glycolaldehyde, and formaldehyde, respectively, with a sampling/analysis cycle time of 30 min. The method has been successfully deployed at a rural site in Pinnacle State Park in Addison, NY, for a 5 week period during the summer of 1998. The ambient concentration means (medians) were 372 (332), 301 (323), and 2040 (2030) pptv for hydroxyacetone, glycolaldehyde, and formaldehyde, respectively. A late-afternoon maximum and an early morning minimum were observed in the diurnal concentration distributions of all three carbonyl compounds. Good correlations among the three carbonyl compounds suggest that they originated from a common source, i.e., photochemical oxidation of biogenic hydrocarbons. Formaldehyde photolysis accounted for about 23% of the total radical photoproduction, whereas contributionsfrom hydroxyacetone and glycolaldehyde photolysis were insignificant because of the much slower photolysis and lower concentrations of these compounds. PMID- 19475946 TI - Indirect photodegradation of amine drugs in aqueous solution under simulated sunlight. AB - The photodegradation of the widely used amine drugs including primary amine (mexiletine), secondary amine (propranolol, phenytoin), and tertiary amine (diphenhydramine, antipyrine) were investigated in the presence of nitrate and humic substances under simulated sunlight. All of the amine drugs were photodegraded by nitrate due to the attack of hydroxyl radicals (*OH). The bimolecular rate constants for the reaction between each amine drug and *OH ranged from (2.1 +/- 0.2) x 10(9) to (8.7 +/- 0.3) x 10(9) M(-1) s(-1). In contrast, only mexiletine, propranolol, and diphenhydramine were selectively photodegraded in the presence of humic substances (HS). Fulvic acid was a more efficient sensitizer than humic acid throughout. The HS triplet states were verified to be main reactive species in the photochemical reaction. Furthermore, an electron transfer mechanism for the reaction with the HS triplet states was proposed on the basis of all information obtained under a series of experiments. The electron transfer from the nonbonding electrons on nitrogen (N-electrons) of the amine drugs to the excited ketone of the HS occurred. The availability of N electrons and presence of hydrogen on carbon alpha of amine (alpha-hydrogen) were two key factors for the electron-transfer interaction. Moreover, the photoproducts were identified by GC-MS and the degradation pathways were proposed. The results strongly suggest the impact of humic substances on the photochemical fate of amine drugs in the natural waters. PMID- 19475947 TI - Effect of NO2 concentration on product yields of the gas-phase NO3 radical initiated reaction of ethyl- and dimethyl-naphthalenes. AB - Alkylnaphthalenes are minor constituents of vehicle fuels and are emitted into the atmosphere in vehicle exhaust and other sources of incomplete combustion. In the lower atmosphere, alkylnaphthalenes react with OH radicals during daylight hours and with NO3 radicals during evening and nighttime, and both radical initiated reactions have been postulated to explain ambient alkylnitronaphthalene profiles. To obtain insight into the NO3 radical reaction mechanism, we have investigated the formation of potentially genotoxic ethyl- and dimethyl nitronaphthalenes and quinones, as well as aromatic carbonyls, from the NO3 radical-initiated reactions of ethylnaphthalenes (ENs) and dimethylnaphthalenes (DMNs) over the NO2 concentration range approximately 0.2-2 ppmV. Our results for the formation of alkylnitronaphthalenes are consistent with gas-phase NO3 radical initiated reactions being a source of alkylnitronaphthalenes in ambient air, and it appears that quinone formation from the gas-phase nighttime reactions of NO3 radicals with 2,6- and 2,7-DMN may be important in the atmosphere and warrants further investigation. PMID- 19475948 TI - Microorganisms and explosives: mechanisms of nitrogen release from TNT for use as an N-source for growth. AB - Unstable reduced derivatives of 2,4,6-trinitrotoluene (TNT) produced by microorganisms have been found to release nitrite by rearomatization and/or condensation. Here, we present further information regarding the novel mechanism of the condensation of reactive hydroxylaminodinitrotoluene and the Meisenheimer dihydride complex of TNT to produce two secondary diarylamine isomers. Using uniformly 15N-labeled (15N3) TNT, we show that the nitrite is being released by the condensation reaction and, also under environmental conditions, will originate from the microbiologically generated dihydride complex. PMID- 19475950 TI - Effect of stratospheric aerosols on direct sunlight and implications for concentrating solar power. AB - Light scattering calculations and data show that stratospheric aerosols reduce direct sunlight by about 4 W for every watt reflected to outer space. The balance becomes diffuse sunlight. One consequence of deliberate enhancement of the stratospheric aerosol layer would be a significant reduction in the efficiency of solar power generation systems using parabolic or other concentrating optics. There also would be a reduction in the effectiveness of passive solar design. PMID- 19475949 TI - Mechanisms associated with the high adsorption of dibenzo-p-dioxin from water by smectite clays. AB - Clay minerals may be an important unrecognized sorptive phase for dioxins in soils and clay deposits. Smectites, especially Cs-saponite, effectively adsorbed dibenzo-p-dioxin (DD) from water, reaching 0.8% (wt/wt). Adsorption was promoted by exchangeable cations with low hydration energies, and negative charge in the smectite arising from the tetrahedral siloxane sheets. X-ray diffraction measurements revealed that as DD loading increased to > or =8000 mg/kg the clay basal spacing increased abruptly from 12.3 to 15.2 A demonstrating DD intercalation. The 12.3 A spacing provides an interlayer distance that closely matches the molecular thickness of DD. In this configuration DD is essentially dehydrated as it interacts with the opposing hydrophobic siloxane sheets and with coplanar Cs+ via one of the dioxin ring oxygens. Ab initio calculations suggest that geometrical structures form at higher loadings in which intercalated DD molecules adopt a butterfly geometry sandwiched between dehydrated interlayer Cs+ and the siloxane surface, consistent with the 15.2 A spacing, wherein Cs+ interacts with dioxin ring oxygens and benzene ring pi-electrons. Fourier transformation infrared measurements confirm that adsorbed DD is present in orientations that are not parallel with the interlayer planar siloxane surfaces of smectite. PMID- 19475951 TI - Effects of coating of dicarboxylic acids on the mass-mobility relationship of soot particles. AB - Atandem differential mobility analyzer (TDMA) and a differential mobility analyzer-aerosol particle mass analyzer (DMA-APM) have been employed to study morphology and hygroscopicity of soot aerosol internally mixed with dicarboxylic acids. The effective densities, fractal dimensions, and dynamic shape factors of soot particles before and after coating with succinic and glutaric acids are determined. Coating of soot with succinic acid results in a significant increase in the particle mobility diameter, mass, and effective density, but these properties recover to their initial values once succinic acid is removed by heating, suggesting that no restructuring of the soot core occurs. This conclusion is also supported from the observation of similar fractal dimensions and dynamic shape factors for fresh and coated/heated soot aggregates. Also, no change is observed when succinic acid-coated aggregates are cycled through elevated relative humidity (5% to 90% to 5% RH) below the succinic acid deliquescence point. When soot is coated with glutaric acid, the particle mass increases, but the mobility diameter shrinks by 10-40%. Cycling the soot aerosol coated with glutaric acid through elevated relative humidity leads to an additional mass increase, indicating that condensed water remains within the coating even at low RH. The fractal dimension of soot particles increases after coating and remains high when glutaric acid is removed by heating. The dynamic shape factor of glutaric acid-coated and heated soot is significantly lower than that of fresh soot, suggesting a significant restructuring of the soot agglomerates by glutaric acid. The results imply that internal mixing of soot aerosol during atmospheric aging leads to changes in hygroscopicity, morphology, and effective density, which likely modify their effects on direct and indirect climate forcing and deposition in the human respiratory system. PMID- 19475952 TI - Isotopic fractionation of methyl tert-butyl ether suggests different initial reaction mechanisms during aerobic biodegradation. AB - Carbon isotopic enrichment factors (epsilonC) measured during cometabolic biodegradation of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and tert-amyl methyl ether (TAME) by Pseudonocardia tetrahydrofuranoxydans strain K1 were -2.3 +/- 0.2 per thousand, -1.7 +/- 0.2 per thousand, and -1.7 +/- 0.3 per thousand, respectively. The measured carbon apparent kinetic isotope effect was 1.01 for all compounds, consistent with the expected kinetic isotope effects for both oxidation of the methoxy (or ethoxy) group and enzymatic SN1 biodegradation mechanisms. Significantly, delta13C measurements of the tert-butyl alcohol and tert-amyl alcohol products indicated that the tert-butyl and tert amyl groups do not participate in the reaction and confirmed that ether biodegradation by strain K1 involves oxidation of the methoxy (or ethoxy) group. Measured hydrogen isotopic enrichment factors (epsilonH) were -100 +/- 10 per thousand, -73 +/- 7 per thousand, and -72 +/- 20 per thousand for MTBE, ETBE, and TAME respectively. Previous results reported for aerobic biodegradation of MTBE by Methylibium petroleiphilum PM1 and Methylibium R8 showed smaller epsilonH values (-35 per thousand and -42 per thousand, respectively). Plots of Delta2H/Delta13C show different slopes for strain K1 compared with strains PM1 and R8, suggesting that different mechanisms are utilized by K1 and PM1/R8 during aerobic MTBE biodegradation. PMID- 19475953 TI - Dual-layer hollow fibers with enhanced flux as novel forward osmosis membranes for water production. AB - We have demonstrated in this work the prospect of dual-layer polybenzimidazole polyethersulfone (PBI-PES) nanofiltration (NF) hollow fiber membranes in the forward osmosis (FO) process for water production: The state-of-the-art for dual layer membrane fabrication via coextrusion technology could produce the resultant membrane consisting of an ultrathin selective skin, fully porous water channels underneath, and a microporous sponge-like support structure. Together with its sharp pore size distribution and self-charged PBI selective membrane surface, the dual-layer hollow fiber forward osmosis membrane can achieve a water flux as high as 33.8 L x m(-2) x hr(-1) and a salt flux less than 1.0 g x m(-2) x hr(-1) at room temperature of 23 degrees C using 5 M MgCl2 as the draw solution. A comprehensive literature review of previous efforts on identifying suitable membranes and appropriate draw solutions in the FO process for water production and seawater desalination have also been conducted. It shows that the water fluxes of the dual-layer hollow fiber FO membrane developed in this work utilizing MgCl2 as the draw solutions generally surpasses those FO processes utilizing RO membranes and is comparable to most FO processes using commercial FO membrane and employing other salts or sugar instead of MgCl2 as the draw solutions. PMID- 19475954 TI - Enantiomeric signatures of organochlorine pesticides in Asian, trans-Pacific, and western U.S. air masses. AB - The enantiomeric signatures of organochlorine pesticides were measured in air masses from Okinawa, Japan and three remote locations in the Pacific Northwestern United States: Cheeka Peak Observatory (CPO), a marine boundary layer site on the Olympic Peninsula of Washington at 500 m above sea level (m.a.s.l); Mary's Peak Observatory (MPO), a site at 1250 m.a.s.l in Oregon's Coast range; and Mt. Bachelor Observatory (MBO), a site at 2763 m.a.s.l in Oregon's Cascade range. The enantiomeric signatures of composite soil samples, collected from China, South Korea, and the western U.S. were also measured. The data from chiral analysis was expressed asthe enantiomeric fraction, defined as (+) enantiomer/(sum of the (+) and (-) enantiomers), where a racemic composition has EF = 0.5. Racemic alpha hexachlorocyclohexane (alpha-HCH) was measured in Asian air masses at Okinawa and in Chinese and South Korean soils. Nonracemic alpha-HCH (EF = 0.528 +/- 0.0048) was measured in regional air masses at CPO, and may reflect volatilization from the Pacific Ocean and regional soils. However, during trans-Pacific transport events at CPO, the alpha-HCH EFs were significantly more racemic (EF = 0.513 +/- 0.0003, p < 0.001). Racemic alpha-HCH was consistently measured at MPO and MBO in trans-Pacific air masses that had spent considerable time in the free troposphere. The alpha-HCH EFs in CPO, MPO, and MBO air masses were negatively correlated (p = 0.0017) with the amount of time the air mass spent above the boundary layer, along the 10-day back air mass trajectory, prior to being sampled. This suggests that, on the West coast of the U.S., the alpha-HCH in the free troposphere is racemic. Racemic signatures of cis- and trans-chlordane were measured in air masses at all four air sampling sites, suggesting that Asian and U.S. urban areas continue to be sources of chlordane that has not yet been biotransformed. PMID- 19475955 TI - Enhancement of mercury capture by the simultaneous addition of hydrogen bromide (HBr) and fly ashes in a slipstream facility. AB - Low halogen content in tested Powder River Basin (PRB) coals and low loss of ignition content (LOI) in PRB-derived fly ash were likely responsible for higher elemental mercury content (averaging about 75%) in the flue gas and also lower mercury capture efficiency by electrostatic precipitator (ESP) and wet-FGD. To develop a cost-effective approach to mercury capture in a full-scale coal-fired utility boiler burning PRB coal, experiments were conducted adding hydrogen bromide (HBr) or simultaneously adding HBr and selected fly ashes in a slipstream reactor (0.152 x 0.152 m) under real flue gas conditions. The residence time of the flue gas inside the reactorwas about 1.4 s. The average temperature of the slipstream reactor was controlled at about 155 degrees C. Tests were organized into two phases. In Phase 1, only HBr was added to the slipstream reactor, and in Phase 2, HBr and selected fly ash were added simultaneously. HBr injection was effective (>90%) for mercury oxidation at a low temperature (155 degrees C) with an HBr addition concentration of about 4 ppm in the flue gas. Additionally, injected HBr enhanced mercury capture by PRB fly ash in the low-temperature range. The mercury capture efficiency, attesting conditions of the slipstream reactor, reached about 50% at an HBr injection concentration of 4 ppm in the flue gas. Compared to only the addition of HBr, simultaneously adding bituminous derived fly ash in a minimum amount (30 lb/MMacf), together with HBr injection at 4 ppm, could increase mercury capture efficiency by 30%. Injection of lignite derived fly ash at 30 lb/MMacf could achieve even higher mercury removal efficiency (an additional 35% mercury capture efficiency compared to HBr addition alone). PMID- 19475956 TI - Secondary organic aerosol-forming reactions of glyoxal with amino acids. AB - Glyoxal, the simplest and most abundant alpha-dicarbonyl compound in the atmosphere, is scavenged by clouds and aerosol, where it reacts with nucleophiles to form low-volatility products. Here we examine the reactions of glyoxal with five amino acids common in clouds. When glyoxal and glycine, serine, aspartic acid or ornithine are present at concentrations as low as 30/microM in evaporating aqueous droplets or bulk solutions, 1,3-disubstituted imidazoles are formed in irreversible second-order reactions detected by nuclear magnetic resonance (NMR), aerosol mass spectrometry (AMS) and electrospray ionization mass spectrometry (ESI-MS). In contrast, glyoxal reacts with arginine preferentially at side chain amino groups, forming nonaromatic five-membered rings. All reactions were accompanied by browning. The uptake of 45 ppb glyoxal by solid phase glycine aerosol at 50% RH was also studied and found to cause particle growth and the production of imidazole measured by scanning mobility particle sizing and AMS, respectively, with a glyoxal uptake coefficient alpha = 0.0004. Comparison of reaction kinetics in bulk and in drying droplets shows that conversion of glyoxal dihydrate to monohydrate accelerates the reaction by over 3 orders of magnitude, allowing these reactions to occur at atmospheric conditions. PMID- 19475957 TI - Sorption of Th(IV) onto iron corrosion products: EXAFS study. AB - Long-term performance assessment of nuclear waste repositories is affected by the ability of the outer barrier systems to retain radionuclides after possible corrosive leakage of waste containers. The mobility of the radionuclides released from the spent fuel depends strongly on the processes that take place in the backfill material. The interaction of steel corrosion products and radionuclides is part of such a scenario. In this work, the sorption of Th(IV) onto 2-line ferrihydrite (FeOOH x H2O) and magnetite (Fe3O4), used as models for steel corrosion products, has been studied using EXAFS spectroscopy. Sorption samples were prepared in 0.1 M NaClO4 solutions at acidic pH (initial pH values in the range 3.0-4.2) either from undersaturation and supersaturation conditions with respect to amorphous ThO2. Two oxygen subshells, one at 2.37 A and another at 2.54 A, were observed in the first hydration sphere of Th in the case of the ferrihydrite samples. Th-Fe distances for the different ferrihydrite samples are approximately 3.60 A. These results indicate a corner sharing surface complex of Th(IV) ion onto the ferrihydrite surface where the Th atom shares one O atom with each of two coordinated octahedra. The longer Th-O distance accounts for coordinated water molecules. No significant changes in the structural environment of Th in terms of coordination numbers and distances were detected as a function of Th(IV) concentration. Magnetite samples sorbing Th(IV) also showed also a strong distortion of the O shell, but in contrast to ferrihydrite, two types of nearest Fe atoms were detected at 3.50 A and 3.70 A. These results indicate that Th(IV) ion sorbs onto the magnetite surface as bidentate-corner sharing arrangements to [FeO6] octahedra and [FeO4] tetrahedra. PMID- 19475958 TI - Computerized pathway elucidation for hydroxyl radical-induced chain reaction mechanisms in aqueous phase advanced oxidation processes. AB - The radical reaction mechanism that is involved in advanced oxidation processes is complex. An increasing number of trace contaminants and stringent drinking water standards call for a rule-based model to provide insight to the mechanism of the processes. A model was developed to predict the pathway of contaminant degradation and byproduct formation during advanced oxidation. The model builds chemical molecules as graph objects, which enables mathematic abstraction of chemicals and preserves chemistry information. The model algorithm enumerates all possible reaction pathways according to the elementary reactions (built as reaction rules) established from experimental observation. The method can predict minor pathways that could lead to toxic byproducts so that measures can be taken to ensure drinking water treatment safety. The method can be of great assistance to water treatment engineers and chemists who appreciate the mechanism of treatment processes. PMID- 19475959 TI - Forward modeling of metal complexation by NOM: I. A priori prediction of conditional constants and speciation. AB - An agent-based simulation of the transformations of natural organic matter (NOM) is combined with quantitative structure-property relationships (QSPRs) for conditional metal-ligand binding constants (K'ML at pH 7.0 and ionic strength = 0.10 M) in order to predict metal binding by NOM. The resulting a priori predictions do not rely upon calibration to environmental data, but vary with the precursor molecules and transformation conditions used in the simulation. Magnitudes and distributions of K'ML are consistent with previously reported values. In a simulation starting with tannin, terpenoid, and flavonoid precursors, metal binding decreases in the order Cu(II) approximately equal to Al(III) approximately equal to Pb(II) > Zn(II) approximately equal to Ni(II) > Ca(II) approximately equal to Cd(II), whereas in simulations containing protein precursors (and thus amine-containing ligands), Al(III) is relatively less and Ni(II) and Cd(II) relatively more strongly bound. Speciation calculations are in good agreement with experimental results for a variety of metals and NOM samples, with typical root-mean-square error (RMSE) of approximately 0.1 to approximately 0.3 log units in free or total metal concentrations and typical biases of <0.2 log units in those concentrations. PMID- 19475960 TI - Multimedia modeling of polybrominated diphenyl ether emissions and fate indoors. AB - We adapted an indoor multimedia fugacity model to consider emissions and fate of polybrominated diphenyl ethers (PBDEs) and to understand the variability of indoor concentrations. The model was applied to an office in which an 80% decrease in PBDE air concentration was observed after an old computer was exchanged with a newer one. PBDE-impregnated polyurethane foam (PUF) and carpet were treated as pseudo-steady-state components with specified fugacities derived from measured concentrations of 173 and 2140 ng x g(-1), respectively. Emission rates of 35 and 5.4 ng x h(-1), for the old and new computers, respectively, were calculated using the pseudo-steady-state approach. Particle movement (deposition and resuspension) dominates within-room transport processes, and dust removal (vacuuming) and air advection (ventilation) are the main loss processes. The most sensitive parameters to air concentrations and estimated emission rates are room temperature, particle concentrations and deposition velocity, and air exchange rates. The air exchange rates and bouncing on PUF furniture can alter whether the PUF and carpet are sources or sinks of PBDEs. Model results suggest that exposure via air can be reduced by removing dust, having a high air exchange rate, and low indoor temperatures. PMID- 19475961 TI - A dynamic agent-based analysis for the environmental impacts of conventional and novel book retailing. AB - The dynamics of an e-commerce market and the associated environmental impacts from a bottom-up perspective using an agent-based model is explored. A conceptual meta-theory from psychology is adopted to form the behavioral rules of artificial consumers choosing different methods of buying a book, including conventional bookstores, e-commerce, and a proposed self-pick-up option. Given the energy and emissions savings that result from a shift to e-commerce from bookstore purchase, it appears that reductions in environmental impacts are relatively probable. Additionally, our results suggest that the shift to e-commerce is mainly due to the growth of Internet users, which ties energy and emissions savings to Internet penetration. Moreover, under any scenario, the energy and emissions savings will be provided by the introduction of the proposed self-pick-up option. Our model thus provides insights into market behaviors and related environmental impacts of the growing use of e-commerce systems at the retail level, and provides a basis for the development and implementation of more sustainable policies and practices. PMID- 19475962 TI - A combined food web toxicokinetic and species bioenergetic model for predicting seasonal PCB elimination by yellow perch (Perca flavescens). AB - A commonly used toxicokinetic model was coupled to a bioenergetic submodel optimized for yellow perch and an empirical growth submodel to predict daily PCB elimination flux in three size classes of fish under seasonally variable temperatures. Across seasons, the bioenergetic model predicted highly variable gill ventilation and fecal egestion rates which varied by 74.2-111.2 fold and 35 65 fold, respectively, over the annual cycle. The empirical growth model accounted for seasonal trends in overwintering lipid losses evident for all fish size classes and growth, evident only for the small fish size class, during warm water periods. The toxicokinetic model described seasonal trends in congener specific PCB mass balance of fish, but tended to overestimate PCB elimination for less hydrophobic congeners when the recommended gill transfer efficiency term (Ew) of 0.54 was used. Downward adjustment of Ew to an average value of 0.14 produced the strongest model fit for several low Kow PCBs but had less effect on model performance for mid- to high Kow congeners. The toxicokinetic model was less sensitive to parameters involved in fecal elimination of PCBs when applied to low and mid-Kow PCBs. This study demonstrates the importance of seasonal trends in metabolic rate, growth, and overwintering weight loss as factors that modify PCB toxicokinetics in temperate fish. PMID- 19475963 TI - Comparing polychaete and polyethylene uptake to assess sediment resuspension effects on PCB bioavailability. AB - Polyethylene sampler uptake was compared to polychaete uptake to assess bioavailability of polychlorinated biphenyls (PCBs) from resuspended sediments. New Bedford Harbor (MA, U.S.) sediment contaminated with PCBs, was resuspended under four different water column oxidation conditions: resuspension alone, resuspension under aeration, resuspension under helium, and no resuspension (control). Residuals were tested for differences in PCB availability to the marine polychaete Nereis virens and to polyethylene (PE) passive samplers. Few significant differences between the four resuspension treatments were observed: under aeration, three of 23 PCBs analyzed showed significant increases in polychaete accumulation, while resuspension alone showed increased concentrations in PE samplers for nine of 23 PCBs. Otherwise, no differences were observed and overall we concluded that resuspension had no effect on residual PCB availability. The relationship between disequilibrium-corrected PE and lipid normalized polychaete PCB concentrations was nearly 1:1 with a strong linear correlation (r2 = 0.877), demonstrating PCBs are taken up similarly into PE and lipid. On average, PE samplers suggested dissolved PCB concentrations 3.6 times greater than those calculated with lipid-water partitioning, though on a congener specific basis this was only observed for lower chlorinated PCBs; for higher chlorinated PCBs, PE-water partitioning suggested lower dissolved concentrations than those based on lipid. Organic carbon (OC)-water and OC and black carbon combined (OC+BC)-water partitioning suggested average dissolved concentrations 29 and 10 times greater, respectively, than those estimated with lipid-water partitioning. This demonstrates that PE-measured porewater concentrations can provide a more reliable estimate of bioavailability than sediment geochemistry. PMID- 19475964 TI - Fluorescence spectrophotometer analysis of polycyclic aromatic hydrocarbons in environmental samples based on solid phase extraction using molecularly imprinted polymer. AB - A molecularly imprinted polymer (MIP) was synthesized using a polycyclic aromatic hydrocarbon (PAH) standard as a template, methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker, and acetonitrile as a porogen. This polymer was used as a solid phase adsorbent for the quantitative enrichment of PAHs in coastal sediments, atmospheric particulates, and industrial effluents. The MIP selective adsorption capacity for PAHs started reducing when the chemical oxygen demand (COD) and total dissolved solids (TDS) was more than 800 mg L(-1) in the targeted environmental samples. The adsorption stability of the MIP was tested by the consecutive contact of environmental samples, and it was shown that the performance of the MIP did not vary after 10 enrichments and desorption cycles. Recoveries of eight PAH compounds, extracted from 10 g of coastal sediments and 1 L of industrial effluent spiked with 10 microL of standard PAHs, showed recoveries between 85 and 96%. The fluorescence spectrophotometer limit of detection of PAHs varied from 10 to 30 etag L(-1) in industrial effluent and from 0.1 to 2.9 etag kg(-1) in solid samples (coastal sediment and atmospheric particulates), and this indicates that the environmental analytical method is significantly sensitive, when compared with other commonly used methods such as gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. PMID- 19475965 TI - Fate of Libby amphibole fibers when burning contaminated firewood. AB - In Libby, Montana, over 70 years of mining amphibole-contaminated vermiculite has led to amphibole contamination in areas surrounding the abandoned mine and in other areas throughout the town. In addition to contaminated soils, tree bark has also been found to be contaminated with amphibole fibers throughout the Libby area. As residential woodstoves are the main source of home heating in Libby, the purpose of this study was to determine if amphibole fibers become liberated into the ambient air when amphibole-contaminated firewood is combusted. Amphibole contaminated firewood was combusted in new, EPA-certified stoves during three trials. The results of these trials showed that the majority of the fibers remained in the ash following the combustion process, suggesting that additional potential exposures can occur within the homes to those that clean the ash out of woodstoves. The combustion trials also revealed that amphibole fibers can become liberated into the ambient air during the combustion process. Amphibole fibers were found impacted in the ductwork, as well as detected in wipe samples collected from an inverted container used to concentrate the woodsmoke emissions. These findings stress the need for identifying a clean fuel source for the inhabitants of Libby to prevent future exposures. PMID- 19475966 TI - Speciation analysis of gadolinium chelates in hospital effluents and wastewater treatment plant sewage by a novel HILIC/ICP-MS method. AB - The behavior of Gd chelates used in magnetic resonance imaging (MRI) within the process of sewage treatment is widely unknown. Due to the varying toxicity of the particular Gd species [J. M. Idee et al. Fundam. Clin. Pharmacol. 2006, 20, 563 576], it is important to not only investigate total Gd concentrations, but the Gd species as well. This work describes a novel method for speciation analysis of the most important gadolinium chelates in wastewaters. This novel approach consists of coupling hydrophilic interaction chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS). HILIC/ICP-MS exhibits high separation efficiency for the simultaneous separation of the five predominantly applied MRI contrast agents and the required selectivity and sensitivity for trace determination in wastewater samples. For the first time, the distribution of particular Gd chelate complexes was determined in hospital effluent, municipal sewage, and wastewater treatment plant (WWTP) samples. The data were compared with the total concentration of Gd as determined by ICP-MS. The active compounds of Multihance, Dotarem, and Gadovist were identified in local WWTP samples. Interestingly, the macrocyclic, nonionic compound Gd-BT-DO3A (Gadovist) was found to be the most abundant Gd complex in all investigated samples. This is in contrast to prevalent assumptions that linear ionic Gd chelates such as Gd-DTPA (Magnevist) would be the predominant species [G. Morteani et al. Environ. Geochem. Health 2006, 28, 257-264 and M. Bau and P. Dulski, Earth Planet. Sci. Lett. 1996, 143, 245-255]. Although contrast agent concentrations tend to be reduced during wastewater treatment, Gd-BT-DO3A was still found in WWTP effluents. PMID- 19475967 TI - Quantifying volatile organic compounds in porous media: effects of sampling method attributes, contaminant characteristics and environmental conditions. AB - Understanding how sampling methods can impact the accuracy of volatile organic compound (VOC) measurements in samples of soil and subsurface porous media is often critical to sound decision making during characterization and remediation of VOC contaminated sites. In this study, the accuracy of VOC measurements was investigated using an experimental apparatus packed with sandy porous media and contaminated with known levels of VOCs, which could be sampled using different methods under variable, but controlled, conditions. Five sampling methods were examined representing different degrees of porous media disaggregation and duration of atmospheric exposure (MDE) that can occur during sample acquisition and preservation in the field. Three pervasive VOCs were studied (1,1,1 trichloroethane, trichloroethylene, tetrachloroethylene) at low and high concentration levels. Five porous media temperatures were examined ranging from 5 to 80 degrees C to represent ambient or thermal remediation conditions and two water saturation levels were used to mimic vadose zone and groundwater zone conditions. The results of this research demonstrated that sampling method attributes can impact the accuracy of VOC measurements in porous media by causing negative bias in VOC concentration data ranging from near 0 to 90% or more. The magnitude of the negative bias is dependent on the attributes of the sampling method used (i.e., level of MDE) and interactions with key contaminant properties and environmental conditions (i.e., VOC KH, porous media temperature, water saturation level). PMID- 19475968 TI - Macroscopic and X-ray photoelectron spectroscopic investigation of interactions of arsenic with synthesized pyrite. AB - Interactions of arsenic with synthesized pyrite were investigated using macroscopic (solution phase experiments) and microscopic (X-ray photoelectron spectroscopic investigation) approaches. Arsenic removal by pyrite was strongly dependent on pH and arsenic species. Both arsenite (As(III)) and arsenate (As(V)) had a strong affinity for the pyrite surface under acidic conditions, but As(III) was more effectively removed than As(V). A BET isotherm equation provided the best fit to arsenic removal data, suggesting that surface precipitation occurred at a high arsenic/pyrite ratio. The addition of competing ions did not substantially affect the ultimate distribution of arsenic between the pyrite surface and the solution, but changing the pH affected arsenic stability on pyrite. X-ray photoelectron spectroscopy (XPS) revealed that under acidic conditions, arsenic was removed by reaction with pyrite to form solid phases similar to As2S3 and As4S4. However, under neutral to alkaline conditions, arsenic was removed by sorption and precipitation to form solid phases that are similar to FeAsS and As2S3/As4S4. PMID- 19475969 TI - Potent antibacterial activities of Ag/TiO2 nanocomposite powders synthesized by a one-pot sol-gel method. AB - The antimicrobial properties of Ag-based materials have been actively investigated recently. In such materials, control of the size of the Ag particles is critical to their bactericidal performance. A novel one-pot sol-gel scheme is described here. It incorporates room-temperature ionic liquids (RTILs) to synthesize Ag/TiO2 nanocomposite powders. The presence of RTILs is indispensable to the control of the size of the Ag particles. Highly dispersed, metallic Ag nanoclusters are formed on the TiO2 nanoparticle surface after calcination of the gel. The average cluster size of Ag can be controlled to be below 5 nm with high Ag loading (7.4 wt%). Antibacterial tests using 7.4 wt% Ag/TiO2 on 10(5) CFU/mL Escherichia coli (E. coli) strains incubated on Luria-Bertani (LB)/agar plates show that bacterial growth was inhibited by 98.8% at an Ag concentration of 1.2 microg/mL Complete inhibition was achieved at 2.4 microg(Ag)/mL. At this concentration, a 3.9 wt% Ag/TiO2 sample, with a smaller Ag cluster size (<3 nm), completely inhibited bacterial growth in a more populated E. coli community (approximately 3 x 10(6) CFU/mL). In fact, 1.6 microg/mL Ag suppressed bacterial growth by 99.9% with 3.9 wt% Ag/TiO2. Both the small Ag cluster size and the unique structure of TiO2 nanoparticles supporting highly dispersed Ag clusters are identified to be the sources of a superior bactericidal performance of the RTILs-derived Ag/TiO2. PMID- 19475970 TI - Impact of wastewater treatment processes on organic carbon, organic nitrogen, and DBP precursors in effuent organic matter. AB - Unintentional, indirect wastewater reuse often occurs as wastewater treatment plant (WWTP) discharges contaminate receiving waters serving as drinking-water supplies. A survey was conducted at 23 WWTPs that utilized a range of treatment technologies. Samples were analyzed for typical wastewater and drinking-water constituents, chemical characteristics of the dissolved organic matter (DOM), and disinfection byproduct (DBP) precursors present in the effluent organic matter (EfOM). This was the first large-scale assessment of the critical water quality parameters that affect the formation of potential carcinogens during drinking water treatment relative to the discharge of upstream WWTPs. This study considered a large and wide range of variables, including emerging contaminants rarely studied at WWTPs and never before in one study. This paper emphasizesthe profound impact of nitrification on many measures of effluent water quality, from the obvious wastewater parameters (e.g., ammonia, biochemical oxygen demand) to the ones specific to downstream drinking water treatment plants (e.g., formation potentialsfor a diverse group of DBPs of health concern). Complete nitrification reduced the concentration of biodegradable dissolved organic carbon (BDOC) and changed the ratio of BDOC/DOC. Although nitrification reduced ultraviolet absorbance (UVA) at 254 nm, it resulted in an increase in specific UVA (UVA/DOC). This is attributed to preferential removal of the less UV-absorbing (nonhumic) fraction of the DOC during biological treatment. EfOM is composed of hydrophilic and biodegradable DOM, as well as hydrophobic and recalcitrant DOM, whose proportions change with advanced biological treatment. The onset of nitrification yielded lower precursor levels for haloacetic acids and nitrogenous DBPs (haloacetonitriles, N-nitrosodimethylamine). However, trihalomethane precursors were relatively unaffected by the level of wastewater treatment Thus, one design/operations parameter in wastewater treatment, the decision to have a long enough solids retention time to get reliable nitrification, affected much beyond its immediate goal of ammonium oxidation. PMID- 19475971 TI - Visible-light-Induced photocatalytic oxidation of polycyclic aromatic hydrocarbons over tantalum oxynitride photocatalysts. AB - The photooxidations of five typical polycyclic aromatic hydrocarbons (PAHs) were investigated by using tantalum oxynitride and Pt-tantalum oxynitride as visible light-driven photocatalysts. The electron paramagnetic resonance spin-trap technique and hydrogen peroxide test strip were used to monitor active species formed in these photocatalytic systems. Moreover, the participations of HO*, O2( *) anions, and holes were further examined by adding their scavengers t-butanol, benzoquinone, and iodine anions, respectively. The reaction intermediates were analyzed by gas chromatography-mass spectrometer (GC-MS). The results show that tantalum oxynitride exhibits good photocatalytic activity for the PAHs photodegradation and the activity is greatly promoted by loading cocatalyst Pt. After 6 h visible light irradiation, phenanthrene, anthracene, benzo[a]anthracene, and acenaphthene can be completely oxidized over Pt-tantalum oxynitride. Under UV light irradiation, the photodegradation rate of PHE over Pt tantalum oxynitride is 8 times faster than that over titanium dioxide (P25, 80% anatase, 20% rutile). Oxygen plays a crucial role on the photooxidations of PAHs. t-Butanol and benzoquinone almost have no effect on PAHs photodegradations, which indicate that HO* and O2(-*) anions play a negligible role on the photodegradations of PAHs. However, the presence of iodide anions significantly inhibits these degradation reactions, implying the crucial effect of holes on the photocatalytic systems. The PAHs degradations could therefore be attributed to the formation of holes in these systems. Based on the GC-MS analysis, the possible photooxidation pathways of PAHs were also proposed. PMID- 19475972 TI - Efficacy of constructed wetlands in pesticide removal from tailwaters in the Central Valley, California. AB - Pollutants in agricultural irrigation return flow (tailwater) constitute a significant nonpoint source of pollution in intensive agricultural regions such as the Central Valley of California. Constructed wetlands (CWs) represent a feasible mitigation option to remove pollutants including pesticides in the tailwater. In this study, we evaluated two CWs in the Central Valley for their performance in removing pyrethroid and organophosphate insecticides under field scale production conditions. Both CWs were found to be highly effective in reducing pyrethroid concentrations in the tailwater, with season-average concentration reductions ranging from 52 to 94%. The wetlands also reduced the flow volume by 68-87%, through percolation and evapotranspiration. When both concentration and volume reductions were considered, the season-average removal of pyrethroids ranged from 95 to 100%. The primary mechanism for pyrethroid removal was through sedimentation of pesticide-laden particles, which was influenced by hydraulic residence time and vegetation density. Temporal analysis indicates a potential efficiency threshold during high flow periods. The season average removal of chlorpyrifos ranged 52-61%. The wetlands, however, were less effective at removing diazinon, likely due to its limited sorption to sediment particles. Analysis of pesticide partitioning showed that pyrethroids were enriched on suspended particles in the tailwater. Monitoring of pesticide association with suspended solids and bed sediments suggested an increased affinity of pyrethroids for lighter particles with the potential to move further downstream before subject to sedimentation. Results from this study show that flow-through CWs, when properly designed, are an effective practice for mitigating hydrophobic pesticides in the irrigation tailwater. PMID- 19475973 TI - Continuous high rate anaerobic treatment of oleic acid based wastewater is possible after a step feeding start-up. AB - Mineralization of a synthetic effluent containing 50% COD as oleic acid was achieved in a continuous anaerobic reactor at organic loading rates up to 21 kg COD m(-3) day(-1), HRT of 9 h, attaining 99% of COD removal efficiency and a methane yield higher than 70%. A maximum specific methane production rate of 1170 +/- 170 mg COD-CH4 g VS(-1) day(-1) was measured during the reactor's operation. A start-up strategy combining feeding phases and batch degradation phases was applied to promote the development of an anaerobic community efficient for long chain fatty acids (LCFA) mineralization. Through the start-up period, the methane yield increased gradually from 67% to 91%, and LCFA accumulated onto the sludge only during the first 60 days of operation. For the first time, it is demonstrated that a step feeding start-up is required to produce a specialized and efficient anaerobic community for continuous high rate anaerobic treatment of LCFA-rich wastewater. PMID- 19475974 TI - Advanced oxidation kinetics of aqueous trialkyl phosphate flame retardants and plasticizers. AB - Trialkyl phosphate esters are a class of anthropogenic organics commonly found in surface waters of Europe and North America, due to their frequent application as flame retardants, plasticizers, and solvents. Four trialkyl phosphate esters were evaluated to determine second-order rates of reaction with ultraviolet- and ozone generated *OH in water. Tris(2-butoxyethyl) phosphate (TBEP) was fastest to react with *OH (kOH,TBEP = 1.03 x 10(10) M(-1) s(-1)), followed sequentially by tributyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), and tris(2 chloroisopropyl) phosphate (TCPP) (kOH,TBP = 6.40 x 10(9), kOH,TCEP = 5.60 x 10(8), and kOH,TCPP = 1.98 x 10(8) M(-1) s(-1)). A two-stage process was used to test the validity of the determined kOH for TBEP and the fastest reacting halogenated alkyl phosphate, TCEP. First, *OH oxidation of TCEP and TBEP, in competition with nitrobenzene was measured in ozonated hydrogen peroxide solutions. Applying multiple regression analysis, it was determined that the UV/H2O2 and O3/H2O2 data sets were statistically identical for each compound. The subsequent validated kOH were used to predict TCEP and TBEP photodegradation in neutral pH, model surface water after chemical oxidant addition and UV irradiation (up to 1000 mJ/cm2). The insignificant difference between the predicted TBEP and TCEP photodegradation and a best-fit of the first-order exponential decay function to the observed TBEP and TCEP concentrations with increasing UV fluence was further evidence of the validity of the determined kOH. TBEP oxidation rates were similar in the surface waters tested. Substantial TCEP oxidation in the model surface water required a significant increase in initial H2O2. PMID- 19475975 TI - The pseudophase approach to assessing chemical partitioning in air-water cyclodextrin systems. AB - Henry's Law constants (HLCs) of several common, subsurface hydrophobic organic pollutants (HOPs) including trichloroethylene (TCE), perchloroethylene (PCE) and benzene, toluene, ethylbenzene, and o-xylene (BTEX), were measured using a static headspace phase ratio (SHPR) method over a range of temperatures (35, 45, 55, and 65 degrees C) and experimentally and operationally relevant cyclodextrin (CD) concentrations (0, 10, 20, 50, and 100 g L(-1)). In aqueous CD solutions, HLC values decrease according to a power law relationship with increasing CD concentration due to an apparent solubility enhancement caused by HOP partitioning to the hydrophobic cavity of CD molecules. The temperature dependence of air-water partitioning under the influence of CD was well described by the van't Hoff equation for all HOPs tested. A three-phase equilibrium model was used to interpret air-water-CD partitioning data, treating CD as a pseudophase. Our results show that HOP CD-water partition coefficients decrease linearly with increasing temperature. CD-water partition coefficients were generally independent of CD concentration, with a few exceptions. Comparison of our results for hydroxypropyl-beta-CD and TCE to those from another study showed several major discrepancies, which were attributed to differences in the experimental methods employed. Our attempt to correlate CD-water partition coefficients with HOP chemical properties indicates that correlations based on individual chemical descriptors (e.g., aqueous solubility, octanol-water partition coefficient, molecular volume or ET (30) polarity index) will not be sufficient to obtain accurate estimates of HOP CD-water partition coefficients for other compounds with differing chemical structures. PMID- 19475976 TI - Effect of sludge age on the bacterial diversity of bench scale sequencing batch reactors. AB - Sludge age or mean cell residence time (MCRT) plays a crucial role in design and operation of wastewater treatment plants. The change in performance, for example micropollutant removal, associated with changes in MCRT is often attributed to changes in microbial diversity. We operated four identical laboratory-scale sequencing batch reactors (two test and two control) in parallel for 212 days. Sludge age was decreased gradually (from 10.4to 2.6 days) in experimental reactors whereas it was kept constant (10.4 days) in control reactors. The reactor performance and biomass changed in a manner consistent with our understanding of the effect of sludge age on a reactors performance: the effluent quality and biomass declined with decreasing MCRT. The composition of the bacterial and ammonia-oxidizing bacterial communities in four reactors was analyzed using denaturing gradient gel electrophoresis (DGGE), and similarities in band patterns were measured using the Dice coefficient. The overall similarity between the communities in reactors run at different sludge ages was indistinguishable from the similarity in communities in reactors run at identical sludge ages. This was true for both the general bacterial communities and putative AOB communities. The number of detectable bands in DGGE profiles was also unaffected by sludge age (p approximately 0.5 in both cases). Initially, the detectable diversity of activated sludge communities in all four reactors clustered with time, regardless of their designation or sludge age; however, these clusters were only weakly supported by bootstrap analysis. However, after 135 days, a sludge age specific clustering was observed in the bacterial community but not the putative ammonia-oxidizing bacterial community. The mean self-similarity of each reactor decreased, variance increased, and the number of detectable bands in DGGE profiles decreased over time in all reactors. The changes observed with time are consistent with ecological drift. Sludge age has a subtler and slower effect than we anticipated. However, we postulate that sludge age may be more evident in the taxa occurring below the detection limit of DGGE. New sequencing technology may help us address this hypothesis. PMID- 19475977 TI - Bench-scale studies of in-duct mercury capture using cupric chloride-impregnated carbons. AB - A brominated activated carbon (Darco Hg-LH) and cupric chloride-impregnated activated carbon (CuCl2-ACs) sorbent have been tested in a bench-scale entrained flow reactor system which was developed for simulating in-flight mercury capture in ducts upstream of particulate matter control devices. The bench-scale experimental system has been operated with the conditions of a residence time of 0.75 s and a gas temperature of 140 degrees C to simulate typical conditions in the duct of coal-fired exhaust gas. In addition, sorbent deposition on walls which can occur in a laboratory-scale system more than in a full-scale system was significantly reduced so that additional mercury capture by the deposited sorbent was minimized. In the entrained-flow system, CuCl2-ACs demonstrated similar performance in Hg adsorption and better performance in Hg0 oxidation than Darco Hg-LH. In addition, the carbon content of those sorbents was found to determine their Hg adsorption capability in the entrained-flow system. The bench-scale entrained-flow system was able to demonstrate the important Hg adsorption and oxidation characteristics of the tested sorbents. PMID- 19475978 TI - Increased pollution-induced bacterial community tolerance to sulfadiazine in soil hotspots amended with artificial root exudates. AB - Sulfadiazine (SDZ) residues constitute an important pollutant in soils that may increase environmental reservoirs of antibiotic resistance. Our primary aim was to compare the development of pollution-induced community tolerance (PICT) to SDZ concentration levels in bulk soil and nutrient amended soil hotspots. Agricultural soil microcosms were amended with different concentrations of SDZ with or without weekly additions of artificial root exudates corresponding to realistic rhizodeposition rates. Bacterial community tolerance to SDZ residues, as determined by the [3H]leucine incorporation technique, increased progressively with elevated SDZ exposure, and was significantly increased in soil hotspots (LOEC of 1microg kg(-1)). An alternative PICT approach based on single-cell esterase probing by flow cytometry failed to demonstrate SDZ impacts. Bacterial growth rates ([3H]leucine incorporation) were significantly reduced in both bulk soil and hotspots 24 h after amendment with environmentally relevant concentrations of SDZ, while soil respiration remained unaffected even at 100 microg SDZ g(-1). Our study for the first time demonstrates a drastically increased PICT response of a soil bacterial community due to increased carbon substrate amendment per se. Hence, hotspot soil environments such as rhizosphere and manure-soil interfaces may comprise key sites for proliferation of bacteria that are resistant or tolerant to antibiotics. PMID- 19475979 TI - Biological uptake and depuration of carbon nanotubes by Daphnia magna. AB - It is inevitable that carbon nanotubes (CNTs) will be released to and widely dispersed in environmental ecosystems, given their numerous expected applications. Determination of their potential for bioaccumulation by ecological receptors is thus critical. Previous, research involving several different terrestrial and benthic organisms has indicated that CNTs spiked to soils or sediments do not bioaccumulate. Conversely, we report here distinctly different uptake and depuration behaviors for an aquatic organism, Daphnia magna, in a water-only system. After 48 h of exposure of this organism to a 0.4 microg/mL solution of dispersed nanotubes, the CNTs comprised 6.3 +/- 1.5% of the residual organism dry mass. Moreover, these organisms were unable to excrete the nanotubes to either clean artificial freshwater or filtered Lake Kontiolampi water after 24 h depuration periods, even though the lake water had a substantial concentration of natural organic matter. Addition of algae to the water during the depuration period did result however in release of a significant fraction (approximately 50 85%) of the accumulated CNTs within the first few hours, but little thereafter. Light microscopy results suggest that the vast majority of the accumulated CNTs remained in the organisms' guts and were not absorbed into cellular tissues. PMID- 19475980 TI - Estrogenic wastewater treatment works effluents reduce egg production in fish. AB - Estrogenic chemicals found within wastewater treatment work (WwTW) effluents have been shown individually to inhibit reproduction in fish, but the impact of the WwTW effluents themselves and the complex mixtures of environmental estrogens and other endocrine disrupting chemicals they contain has not been established. In this investigation, the effect of exposure to three WwTW effluents, with differing levels of estrogenic activity, was assessed on egg production in pair breeding fathead minnow. Exposure to two of the three effluents tested resulted in a reduced egg production (by 28% for effluent I at a dilution of 50% and by 44% for effluent III at full strength), which was proportional to the estrogenic content of the effluents. The test effluents, however, had a greater effect on egg production than might be expected, on the basis of both the response they induced for induction of vitellogenin (an estrogen exposure biomarker) and when compared with an equivalent estrogen exposure to EE2. These data show that reliance on relatively simple biomarker responses for estrogenic activity alone, such as vitellogenin, can significantly underestimate the impacts of estrogenic WwTW effluents on fitness parameters such as reproductive health that are regulated by more complex estrogenic (and other endocrine) signaling mechanisms. PMID- 19475982 TI - Comment on "Tracking petroleum refinery emission events using lanthanum and lanthanides as elemental markers for PM2.5". PMID- 19475981 TI - Projections of global mercury emissions in 2050. AB - Global Hg emissions are presented for the year 2050 under a variety of assumptions about socioeconomic and technology development. We find it likely that Hg emissions will increase in the future. The range of 2050 global Hg emissions is projected to be 2390-4860 Mg, compared to 2006 levels of 2480 Mg, reflecting a change of -4% to +96%. The main driving force for increased emissions is the expansion of coal-fired electricity generation in the developing world, particularly Asia. Our ability to arrest the growth in Hg emissions is limited by the relatively low Hg removal efficiency of the current generation of emission control technologies for coal-fired power plants (flue-gas desulfurization). Large-scale deployment of advanced Hg sorbent technologies, such as Activated Carbon Injection, offers the promise of lowering the 2050 emissions range to 1670-3480 Mg, but these technologies are not yet in commercial use. The share of elemental Hg in total emissions will decline from today's levels of approximately 65% to approximately 50-55% by 2050, while the share of divalent Hg will increase. This signals a shift from long-range transport of elemental Hg to local deposition of Hg compounds-though emissions of both species could increase under the worst case. PMID- 19475983 TI - Monoterpene hydrocarbons may serve as antipredation defensive compounds in Boisea trivittata, the boxelder bug. AB - Boxelder bugs, Boisea trivittata, are deterred from predation by green anoles (Anolis carolinensis). Hydrodistillation and GC-MS analysis reveals B. trivittata to contain the volatile monoterpene hydrocarbons beta-pinene (83.9%), limonene (14.7%), myrcene (0.8%), and (E)-beta-ocimene (0.6%). The presence of these antifeedant volatile chemicals may serve to provide some protection of boxelder bugs from predation. PMID- 19475984 TI - Three novel sesquiterpene esters from Celastrus angulatus. AB - Three new sesquiterpene polyol esters with a beta-dihydroagarofuran skeleton, NW12 (1), NW27 (2), and NW31 (4), together with a known compound, NW30 (3), were isolated from the root bark of Celastrus angulatus. Their chemical structures were elucidated by analyses of MS and NMR spectral data. Preliminary insecticidal and antitumor activities of these compounds were evaluated. Compounds 1-4 showed moderate stomach toxicity against Mythimna separata, and their KD50 values were 673.6, 1121.3, 1720.0 and 548.6 microg/g, respectively. Only 1 and 3 exhibited slight antitumor activity against human breast cancer cell line (Bcap-37), and their IC50 values were all above 50 microM. PMID- 19475985 TI - Sesquiterpenes with quinone reductase-inducing activity from Liriodendron chinense. AB - Bioassay-directed separation of the methylene chloride extracts from the wood of Liriodendron chinense led to the isolation of six sesquiterpenes, tulipinolide (1), alpha-liriodenolide (2), beta-liriodenolide (3), lipiferolide (4), 11,13 dehydrolanuginolide (5), and tulipinolide diepoxide (6). Compounds 1-6 have not been found previously in L. chinense. The structures of the compounds were established on the basis of NMR spectroscopic data. All the compounds exhibited quinone reductase (QR)-inducing activity in Hepa lclc7 cells. PMID- 19475986 TI - First evidence for an anxiolytic effect of a diterpenoid from Salvia cinnabarina. AB - The potential anxiolytic and anti-depressive activity of CMP1 was studied in the elevated plus-maze test and in the forced swimming test. Furthermore, CMP1 sedative activity was evaluated in pentobarbital treated animals; the effect of CMP1 on spontaneous motor activity (total locomotion) was also evaluated. Our data show that CMP1, at doses that did not affect locomotion, was able to induce anxiolytic and sedative, but not anti-depressive effects. In conclusion, our results represent first evidence for an anxiolytic activity of this diterpenoid from Salvia cinnabarina. PMID- 19475987 TI - Variation of major limonoids in Azadirachta indica fruits at different ripening stages and toxicity against Aedes aegypti. AB - The azadirachtin, salannin, nimbin, deacetylnimbin, azadiradione and epoxyazadiradione contents were determined by HPLC in the fractions prepared from the kernel of neem fruits (Azadirachta indica) collected at different ripening stages. The fully mature fruit (yellow fruits) kernels contained the highest concentration of azadirachtin, nimbin and salannin, whereas the concentration of azadiradione (NC) and epoxyazadiradione (NL) was high in the unripe green berries. The toxicity of the fractions (KEA-1 to KEA-5) obtained from the kernels collected at successive intervals, as well as of the pure limonoids referred to above was evaluated against 3rd instar larvae of Aedes aegypti L. (wild strain). It was observed that the toxicity of these fractions increased with the maturity of the fruits. An interesting observation was that the toxicities of KEA-3 to KEA 5 are comparable and the concentration of all the major limonoids is optimum in KEA-3, which suggested that these exert a joint effect against Aedes aegypti. PMID- 19475988 TI - Cycloartane-type glycosides from two species of Astragalus (Fabaceae). AB - Three known cycloartane-type glycosides were isolated from the roots of two different species of Astragalus, A. glycyphyllos, A. sempervirens. The identification of these compounds were mainly achieved by 2D NMR spectroscopic techniques and FAB-MS. The results of our studies confirm that triterpene saponins from the cycloartane-type skeleton might be chemotaxonomically significant to the genus Astragalus. PMID- 19475989 TI - Glycowithanolides accumulation in in vitro shoot cultures of Indian ginseng (Withania somnifera Dunal). AB - Phytochemical investigations of multiple shoot cultures of selected accessions AGB002 and AGB025 of Withania somnifera established in vitro utilizing shoot tip apices cultured on Murashige and Skoog's medium supplemented with BAP (1 mg/L) have been carried out. This has lead to isolation of four glycowithanolides viz. Withanoside IV (WSG-3), Withanoside VI (WSG-3A), Physagulin D (WSG-P) and Withastraronolide (WSC-O). The structures of these have been confirmed on the basis of spectroscopic data. Multiple shoot cultures could be an alternative renewable resource for production of these biologically active molecules. PMID- 19475990 TI - Structure activity studies on the crinane alkaloid apoptosis-inducing pharmacophore. AB - The apoptosis-inducing ability of alpha-ethano bridged crinane alkaloids was investigated using natural and semi-synthetic derivatives uncovering novel structural requirements of this cytotoxic pharmacophore. An alpha-ethano bridge is required; an alpha- or beta-methoxy or hydroxyl H-bond acceptor are all tolerated at C-3; a small substituent (H, or OH) alone is tolerated at C-11; and a C-1 to C-2 double bond is shown to modulate, but is not a requirement for, apoptosis-inducing activity. PMID- 19475991 TI - HPLC and NMR studies of phenoxazone alkaloids from Pycnoporus cinnabarinus. AB - Crude extracts of the red-orange, bracket fungus Pycnoporus cinnabarinus, collected from five distinct Australian localities were subjected to a chemical and biological profiling study. Subsequent detailed investigation of two of these specimens resulted in the isolation of the new phenoxazone alkaloid, pycnoporin (8), together with cinnabarin (1), tramesanguin (2), and cinnabarinic acid (3). Ergosterol peroxide (11) was also identified from one of the specimens studied. Compounds 1-3 and 8 were elucidated by detailed spectroscopic analyzes, which included the application of elevated temperature-controlled NMR experiments. In addition to the isolation and characterization of 8, this study describes the first successful HPLC purification strategy and complete 2D NMR spectroscopic characterization of compounds 1-3. Also reported are the antioxidant and antiinflammatory activities of the crude extracts of one of the P. cinnabarinus specimens. Compounds 1-3, 8 and 11 displayed varying degrees of antitumor activity while ergosterol peroxide (11) also showed slight antimicrobial and antiviral activities. This is the first report documenting the significant antitumor activity of cinnabarin (1). PMID- 19475992 TI - A new pyranone derivative from the leaves of Livistona australis. AB - A new pyranone derivative, 3-hydroxy-2-(4-hydroxyphenyl)-6-methyl-4H-pyran-4-one (1), was isolated from the leaves of Livistona australis. The structure was determined by NMR spectral analysis. PMID- 19475993 TI - Isolation, structure elucidation and apoptosis-inducing activity of new compounds from the edible fungus Lentinus striguellus. AB - Three new natural compounds, striguellolide A (1), striguellol A (2) and striguellone A (6), together with three known ones, 3,4-trans-dihydroxy-6-methoxy 2,2-dimethylchroman (3), 3-hydroxy-6- methoxy-2,2-dimethylchroman-4-one (4) and 3 hydroxy-6- methoxy-2,2-dimethylchroman (5), were isolated from the agar cultures of the edible fungal strain Lentinus striguellus. Their structures were elucidated by spectroscopic and mass spectrometric analyses, including 1D-, 2D NMR and HR-ESI-Q-TOF-MS, and chemical reactions. Striguellone A showed cytotoxicity against HeLa cells by MTT assay and was found to be an activator of apoptosis, assessed by morphological observation and cell cycle analysis using the flow cytometer. PMID- 19475994 TI - New benzophenone O-glucoside from Hypericum ellipticum. AB - Examination of the acetone extract of the aerial parts of Hypericum ellipticum afforded a new acetylated benzophenone glucoside (3'-O-beta-D-3",4",6" triacetylglucopyranosyl-2,4,5',6-tetrahydroxybenzophenone) together with catechin and epicatechin. The structure of the benzophenone glucoside was determined by 2D NMR spectroscopic data. The compound inhibited the proliferation of CNS tumor cell line (SF-268) and lipid peroxidation in in vitro assays. PMID- 19475995 TI - Structures of new phenolic glycosides from the seeds of Cucurbita moschata. AB - A new phenolic glycoside and three known compounds were isolated from the seeds of Cucurbita moschata. The structures of the new compound was elucidated as phenylcarbinyl 5-O-(4-hydroxy)benzoyl-beta-D-apiofuranosyl (1-->2)-beta-D glucopyranoside on the basis of spectroscopic analysis and chemical evidence. Three known compounds were identified as 1-O-benzyl[5-O-benzoyl-beta-D apiofuranosyl(1-->2)]-beta-D-glucopyranoside 2, cucurbitosides C 3 and A 4, by comparison of the spectral data with reported data. Compound 2 was isolated from this plant for the first time. PMID- 19475996 TI - Myricarborin A and n-butyl-alpha-L-rhamnopyranoside, two novel compounds from the bark of Myrica rubra. AB - From the bark of Chinese Myrica rubra (Myricaceae) two novel compounds, myricarborin A and n-butyl-alpha-L-rhamnopyranoside, have been isolated along with (+)-S- myricanol, (-)-R- myricanol 5-O-beta-D-(6'-O-galloyl)-glucopyanoside and n-butyl-beta-D-fructopyranoside. The structures of the novel compounds were determined by spectroscopic methods. PMID- 19475997 TI - Induction of neuronal differentiation in neurosphere stem cells by ellagic acid derivatives. AB - A bioassay-guided fractionation of methanol extracts of stem barks, combined with screening based on Epidermal Growth Factor (EGF)-responsive neural stem cells (erNSCs) differentiation assay, has been used. This study resulted in the isolation of 3,3'-di-O-methylellagic acid 1, 3,3'-di-O-methyl ellagic acid-4-O beta-D-xylopyranoside 2, ellagic acid 3, and arjunolic acid 4. Among them, compounds 1 and 2 exhibit potent induction of neuronal differentiation in neurosphere stem cells with no cytotoxic effect. These results indicate that compounds 1 and 2 may be useful as pharmacological agents for the treatment of neurodegenerative diseases. These compounds may account, for the use of T. superba in folk medicine for nervous system and mental disorders. PMID- 19475998 TI - Synthesis and characterization of novel cardanol based benzoxazines. AB - Benzoxazines are a class of phenolic compounds extensively studied in polymer science because of their properties as fiber reinforcements, fire-retardants and curing agents. In this article is described a solvent-less process, based on a Mannich reaction involving a primary amine and an aldehyde, for the preparation of new benzoxazines deriving from cardanol (a well known phenol obtained as a renewable organic resource and harmful by-product of the cashew industry). Particular attention is given to the synthesis and chemical characterization (both by 1H NMR spectroscopy and HPLC), while the thermal polymerization process has been monitored by differential scanning calorimetry. PMID- 19475999 TI - Antioxidant and larvicidal activities of Tephrosia egregia Sandw against Aedes aegypti. AB - The antioxidant and larvicidal activities of Tephrosia egregia extracts and its major component, dehydrorotenone, were studied. High antioxidant activity was found for dehydrorotenone and methanol and ethyl acetate extracts from roots and stems, respectively. Among the tested extracts, the hexane extract from stems showed potent larvicidal activity (LC50 12.88 +/- 0.64) while low activity was found for dehydrorotenone. PMID- 19476000 TI - Phenolic compounds from Hypericum calycinum and their antioxidant activity. AB - From the MeOH extract of Hypericum calycinum, two caffeoylquinic acid derivatives, butyl chlorogenate (1), and chlorogenic acid (2), seven flavonoids, quercetin (3), quercitrin (4), hyperoside (5), isoquercitrin (6), miquelianin (7), rutin (8) and I3,II8-biapigenin (9) and two flavanols, (+)-catechin (10) and (-)-epicatechin (11) were isolated. Identification of the isolates was carried out by spectroscopic analysis including 1D and 2D NMR experiments as well as mass spectrometry. Free radical scavenging activities of the isolated compounds were determined in in-vitro 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging models. The compounds showed strong DPPH and moderate NO scavenging activities in a concentration dependent manner. (+)-Catechin and (-)-epicatechin were found to be the most active compounds with IC50 values of 4.16 and 4.67 microM for DPPH and 190 and 170 microM for NO scavenging activities, respectively. PMID- 19476001 TI - Phenolic profile and antioxidant evaluation of Mentha x piperita L. (peppermint) extracts. AB - Seven extracts were prepared from Mentha x piperita (peppermint) leaves in sequence using a Soxhlet apparatus, viz. (40-60 degrees) light petroleum (PE), dichloromethane (CH2Cl2), acetonitrile (ACN), ethyl acetate (EtOAc), methanol (MeOH), n-butanol and water (H2O) extracts. The phenolic and flavonoid content of each extract were estimated using spectrophotometric methods whilst a qualitative quantitative analysis was made by reverse-phase high performance liquid chromatography coupled with photodiode array detection (HPLC-PDA). Each extract was assessed in a battery of six antioxidant-related assays so as to determine their iron(III) reductive, iron(II) chelating and free radical scavenging abilities. The MeOH-soluble extract contained the greatest content of total phenols and flavonoids based upon the Folin-Ciocalteu and 2-aminoethyl diphenylborate reagent data and HPLC-PDA analysis. Based upon the chromatographic and UV-spectral data, the leaves principally contained the cinnamic acid caffeic acid, the depside rosmarinic acid and flavonoids (flavones and flavanones). Eriocitrin (383.3 +/- 2.2 mg/g extract) and rosmarinic acid (381.2 +/- 1.9 mg/g extract) were the most abundant components identified within the leaves, whilst naringenin-7-O-glucoside (0.8 +/- 0.01 mg/g extract) was the least abundant component identified being found only in the EtOAc-soluble extract. The EtOAc, ACN and H2O-soluble extracts demonstrated the most potent iron(III) reductive and 1,1'-diphenyl-2-picrylhydrayl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) and hydroxyl free radical scavenging properties; however, the H2O and CH2Cl2 soluble extracts were the most potent extracts in the beta-carotene-linoleic acid bleaching inhibition assay. In terms of iron(II) chelation--an important antioxidant property--the PE, MeOH and H2O extracts demonstrated moderate iron(II) chelating activity. PMID- 19476002 TI - Anti-inflammatory potential and fatty acid content of lipophilic leaf extracts of four Staphylea L. species. AB - Staphylea preparations are used in TCM and have been used by native Americans for a number of indications, such as rheumatism. Based on this knowledge, the anti inflammatory activity of light petroleum extracts of leaves of Staphylea colchica Stev., S. elegans Zab., S. holocarpa Hemsl. and S. pinnata L. has been determined using in vitro assays for inhibition of cyclooxygenase (COX-1 and COX-2) and leukotriene B4 (LTB4) formation by lipoxygenase (5-LOX). All extracts inhibited COX-1 and COX-2, with S. holocarpa and S. elegans performing best. Inhibition of LTB4 formation was less pronounced. As unsaturated fatty acids are known to inhibit arachidonic acid metabolism in vitro, the fatty acid content was determined of the active extracts and set in correlation with their activity. Unsaturated fatty acids were found to contribute to the observed COX-2 and LTB4 formation inhibitory activity to a different extent. PMID- 19476003 TI - Structural characterization of dietary fiber of green chalcumra (Benincasa hispida) fruit by NMR spectroscopic analysis. AB - A water-soluble dietary fiber was isolated from the hot aqueous extract of Chalcumra (Benincasa hispida) fruit. The polysaccharide was found to contain D galactose and D-methyl galacturonate in a molar ratio of 2:1. On the basis of acid hydrolysis, methylation analysis, periodate oxidation, and NMR spectroscopic studies (1H, 13C, TOCSY, DQF-COSY, NOESY, ROESY, HMQC, and HMBC), the repeating unit of the polysaccharide was established as -->4)-beta-D-Galp-(1-->4)-beta-D Galp-(1-->2)-alpha-D-GalpA6Me-( 1-->. PMID- 19476004 TI - A protein containing glucan from an edible mushroom, Termitomyces microcarpus (var). AB - A water-soluble protein containing glucan was isolated from an edible mushroom, Termitomyces microcarpus (var). It was found to contain 55% of carbohydrate and 40% of protein. The protein part was found to consist of glutamine, arginine, isoleucine, leucine and phenylalanine. The structure of the glucan was analyzed on the basis of total acid hydrolysis, methylation, periodate oxidation and NMR studies (1H, 13C, TOCSY, DQF-COSY, NOESY, and HMQC), and the repeating unit of the glucan is established as: --> 6)-alpha-D-Glcp-(1-->. PMID- 19476005 TI - Mutagenesis and genotypic characterization of Aspergillus niger FCBP-02 for improvement in cellulolytic potential. AB - Cellulase is a collective term that encompasses enzymes which catalyze reactions that participate in the degradation of insoluble cellulose to soluble carbohydrates. In the present study, production of extra cellular cellulases by a filamentous fungus, Aspergillus niger FCBP-02, was studied in solid-state fermentation (SSF) as well as in submerged fermentation (SmF). Trials were conducted to evaluate the effect of mutagenesis by UV irradiation (5-40 min) and ethyl methane sulfonate (EMS) treatment (50-300 microg mL(-1)) to obtain hyper active cellulase enzyme producers among the potential strains. The enzyme activity assays of parental and mutant strains clearly revealed significantly higher cellulase activity of mutant A-Ch-5.5 (96 Units mL(-1)), followed by A-UV 5.6 (71 Units mL(-1)) with respect to the wild strain of A. niger FCBP-02 (53.7 Units mL(-1)). The profile of genetic variability among wild and mutant derivatives was scrutinized through RAPD-PCR. The expression pattern of mutants exhibited that the mutants were isogenic variants of the wild type and the out performance of the mutants could be attributed to the change in genetic make up. PMID- 19476006 TI - Enantiomeric composition of (3R)-(-)- and (3S)-(+)-linalool in various essential oils of Indian origin by enantioselective capillary gas chromatography-flame ionization and mass spectrometry detection methods. AB - Enantiomeric ratios of linalool have been determined in various authentic essential oils of Indian origin using 10% heptakis(2,3-di-O-methyl-6-O-tert butyldimethylsilyl)-beta-cyclodextrin as a chiral stationary phase. A complete enantiomeric excess (ee) for (3S)-(+)-linalool was characteristic of Lippia alba and Cinnamomum tamala leaf oils while less than 90% excess was noticed in Zanthoxylum armatum leaf, Zingiber roseum root/rhizome and Citrus sinensis leaf oils. On the contrary, an enantiomeric excess of (3R)-(-)-linalool characterizes essential oils of basil (100% for Ocimum basilicum) and bergamot mint (72 to 75% for Mentha citrata). Notably, some essential oils containing both enantiomers in equal ratios or in racemic forms are rose, geranium, lemongrass and Origanum. The enantiomeric composition studies are discussed as indicators of origin authenticity and quality of essential oil of Indian origin. PMID- 19476007 TI - Essential oil composition of Tanacetum vulgare subsp. siculum (Guss.) Raimondo et Spadaro (Asteraceae) from Sicily. AB - Ninety-four components of the essential oils from aerial parts and capitula of Tanacetum vulgare subsp. siculum (Guss.) Raimondo et Spadaro were detected. Alpha Thujone, beta-thujone and 1,8-cineole were the main constituents of the oils. The analysis allows the assignment of this Tanacetum species to the thujone chemotype. PMID- 19476008 TI - The chemical composition of the essential oils of Euphorbia caracasana and E. cotinifolia (Euphorbiaceae) from Venezuela. AB - The essential oils from leaves of E. caracasana Boiss collected from Miyoi, Pueblo Llano, Merida State at 1800 m above sea level and leaves of E. cotinifolia L collected from Manzano Alto-Ejido, Merida State at 1520 m were analyzed by GC/MS. Beta-Caryophyllene (33.7 %), alpha-humulene (18.8 %) and aromadendrene (8.4 %) were the major constituents of E. caracasana oil, whereas those of E. cotinifolia oil were beta-caryophyllene (39.3 %), germacrene-D (21.5 %) and alpha copaene (9.3 %). PMID- 19476009 TI - Constituents of Cajanus cajan (L.) Millsp., Moringa oleifera Lam., Heliotropium indicum L. and Bidens pilosa L. from Nigeria. AB - The essential oils of four plant species from Nigeria have been extracted by hydrodistillation and analyzed by GC and GC-MS. The oils of Cajanus cajan were comprised of sesquiterpenes (92.5%, 81.2% and 94.3% respectively in the leaves, stem and seeds). The major compounds identified were alpha-himachalene (9.0 11.5%), beta-himachalene (8.0-11.0%), gamma-himachalene (6.9-8.1%), alpha humulene (7.1-8.7%) and alpha-copaene (4.5-5.6%). However, monoterpenoid compounds (81.8%) dominated the oil of Moringa oleifera with an abundance of alpha-phellandrene (25.2%) and p-cymene (24.9%). On the other hand, aldehydes (52.8%) occurred in the highest amount in Heliotropium indicum, represented by phenylacetaldehyde (22.2%), (E)-2-nonenal (8.3%) and (E, Z)-2-nonadienal (6.1%), with a significant quantity of hexahydrofarnesylacetone (8.4%). The leaf and stem oils of Bidens pilosa were dominated by sesquiterpenes (82.3% and 59.3%, respectively). The main compounds in the leaf oil were caryophyllene oxide (37.0%), beta-caryophyllene (10.5%) and humulene oxide (6.0%), while the stem oils had an abundance of hexahydrofarnesyl acetone (13.4%), delta-cadinene (12.0%) and caryophyllene oxide (11.0%). The observed chemical patterns differ considerably from previous investigations. PMID- 19476010 TI - Antimicrobial activity and chemical composition of Senecio sandrasicus on antibiotic resistant staphylococci. AB - The antimicrobial activity of hexane, chloroform, ethyl acetate and ethanol extracts of the aerial parts of S. sandrasicus P.H.Davis (Asteraceae), endemic to Sandras mountain (Turkey), were determined. The antimicrobial activity of the extracts on microorganisms including multi-resistant staphylococci were evaluated using the disc diffusion method. The strains of multi-resistant staphylococci and the other standart bacteria were inhibited by some extracts. The volatile organic compouds of S. sandrasicus was determined by Gas Chromatography (GC) and Gas Chromatography-Mass Spectrometry (GC-MS). The major compounds of hexane extract were aromadendrene oxide 2 (13.3%), spathulenol (12.5%) and beta-caryophylene (11.8%), respectively. PMID- 19476011 TI - Essential oil composition and antimicrobial activity of Ballota nigra L. ssp foetida. AB - The chemical composition of the essential oil of Ballota nigra L. ssp foetida obtained from the flowering aerial parts was analyzed by GC/MS. From the 37 identified constituents of the oil, beta-caryophyllene (20.0%), germacrene D (18.0%) and caryophyllene oxide (15.0%) were the major components. The oil was active against both Gram-negative and Gram-positive bacteria as well as against three Candida species. PMID- 19476012 TI - Nonimmediate allergic reactions induced by drugs: pathogenesis and diagnostic tests. AB - Nonimmediate allergic reactions (NIRs) to drugs, which are the most common reactions induced by specific immunologic mechanisms, can be induced by all commercially available drugs. NIRs can appear hours, days, or even weeks after drug intake. They elicit a spectrum of manifestations, mostly affecting the skin, ranging from maculopapular exanthema and urticaria to other less common but more severe entities such as acute generalized exanthematic pustulosis, drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The main pathologic event involved in NIRs is a T-cell effector response and the wide heterogeneity of clinical symptoms may reflect differences in the underlying immunologic mechanisms. Despite their clinical heterogeneity, NIRs share certain aspects such as the activation of T cells with increased expression of CD25 and HLA-DR. NIRs are classified as type 1 helper (T(H)1) T-cell responses, characterized by the production of interferon-gamma, tumor necrosis factor-alpha, interleukin 2, T bet, and the cytotoxic markers perforin and granzyme B. Diagnosis is often complicated because of the difficulty of obtaining a reliable clinical history, the important role played by cofactors such as viral diseases, and the low sensitivity of skin tests and in vitro tests. Further studies are thus required in order to improve our understanding of NIRs and refine our diagnostic criteria. PMID- 19476013 TI - Diagnosis of immediate-type beta-lactam allergy in vitro by flow-cytometric basophil activation test and sulfidoleukotriene production: a multicenter study. AB - INTRODUCTION: This multicenter study aimed to evaluate the diagnostic value of 2 cellular tests based on basophil reactivity--the basophil activation test (BAT, Flow-CAST) and the sulfidoleukotriene release assay (CAST-ELISA)--in immediate type beta-lactam allergy, particularly in patients with a clinical history of allergy and a negative skin test result. MATERIAL AND METHODS: In a multicenter study encompassing 10 European centers, 181 patients with a history of immediate type beta-lactam allergy, and 81 controls, we evaluated the diagnostic efficiency of specific IgE determinations and of 2 cellular tests based on basophil reactivity, the BAT and the sulfidoleukotriene release assay. RESULTS: With Flow CAST, sensitivity varied for individual beta-lactam allergens from 16% for penicilloyl-polylysine to 33% for amoxicillin, reaching 50% when all 5 allergens were considered. In beta-lactam-allergic patients with negative skin test results (22.8%), Flow-CAST showed positive results for at least 1 of the 5 allergens in 37%. Specificity varied from 89% to 97%, depending on the allergens used. In CAST ELISA, the overall sensitivity in skin test-positive patients was 41.7%; in patients with negative skin test results it was 27.9%. Both tests were not absolutely correlated, so that when all the results were considered together, sensitivity increased to 64.3% and specificity varied for both tests combined from 73% to 92%. In contrast, specific IgE determinations in the same population yielded a lower sensitivity (28.3%). CONCLUSIONS: A diagnostic algorithm including skin tests and specific IgE, followed by cellular tests in negative patients and controlled challenge enabled us to confirm beta-lactam allergy in 92% of cases. This procedure would also allow us to avoid two-thirds of the required controlled challenges. PMID- 19476014 TI - Allergenic profile of nasal polyposis. AB - BACKGROUND: Nasal polyposis is highly prevalent in the general population. Its exact origin is unknown, although several factors are involved in the etiology and development of this condition. Clinical patterns, a history of atopy, environmental exposure, eosinophil-mediated inflammation, the presence of inflammatory mediators, and sensitization to some allergens indicate that nasal polyposis is associated with allergic phenomena. The aim of this study was to identify the association between nasal polyposis and allergic factors by examining hypersensitivity reactions to common allergens and environmental exposure that could lead to the development of atopy. METHODS: We conducted a comparative study of 190 patients with nasal polyposis and 190 healthy individuals. The study included clinical and epidemiological variables, environmental exposure factors, and an allergology workup using skin prick tests with 18 inhaled allergens. RESULTS: A total of 121 patients (63.7%) of the 190 were male; 62.1% had a family history of allergy. The incidence of asthma was 48.9% among the patients and only 2.3% among the controls (P < .001). The factor most frequently involved in the patients' symptoms was weather changes (67.4%). Skin prick tests were positive in 63.2% of the patients and 31.1% of the controls. The allergens that most frequently elicited a reaction from the patients in the prick tests were Dermatophagoides pteronyssinus (27.7%), Dermatophagoides farinae (21.3%), and Olea europaea (21.1%). The difference between these results and those of the controls was statistically significant. CONCLUSIONS: Patients with nasal polyposis are sensitive to the most common allergens in our environment and exhibit a clear-cut correlation with other allergic factors, as confirmed by personal and family histories, the presence of chronic rhinitis, and the results of in vivo tests. PMID- 19476015 TI - Efficacy and safety of desloratadine/pseudoephedrine combination vs its components in seasonal allergic rhinitis. AB - BACKGROUND: Antihistamines are first-line therapy for the treatment of seasonal allergic rhinitis (AR); however, an oral decongestant is often added to improve control of nasal congestion. OBJECTIVE: To examine whether a tablet combining the nonsedating antihistamine desloratadine and the decongestant pseudoephedrine was more effective than either drug administered alone in reducing the symptoms of seasonal AR, including nasal congestion. PATIENTS AND METHODS: In this multicenter, double-blind study, participants (N = 598) with symptomatic seasonal AR were administered either a combination tablet of desloratadine 2.5 mg/pseudoephedrine 120 mg (DL/PSE) bid, a desloratadine 5.0 mg qd and a placebo tablet, or pseudoephedrine 120 mg bid. Participants assessed their symptom severity twice daily over the 2-week treatment period. RESULTS: The primary variable to assess the effects of the antihistamine component--mean change from baseline in average AM/PM reflective total symptom score (TSS), excluding nasal congestion--was significantly greater (-6.54) for DL/PSE than for desloratadine ( 5.09) or pseudoephedrine (-5.07) monotherapy (P < .001 for both). The primary variable to assess the effects of the decongestant component--mean change from baseline in average AM/PM reflective nasal congestion score--was also significantly greater (-0.93) for DL/PSE than for desloratadine (-0.66) or pseudoephedrine (-0.75) (P < .001 vs desloratadine; P = .006 vs pseudoephedrine). CONCLUSION: This study demonstrated that DL/PSE therapy was more effective in reducing symptoms of seasonal AR, including nasal congestion, than the individual components when administered alone, thus supporting use of this combination in participants with symptomatic seasonal AR and prominent nasal congestion. PMID- 19476016 TI - Safety and tolerability of seasonal ultra-rush, high-dose sublingual-swallow immunotherapy in allergic rhinitis to grass and tree pollens: an observational study in 193 children and adolescents. AB - OBJECTIVE: We conducted a large observational study in 193 children and adolescents with allergic rhinitis due to grass or tree pollens to evaluate the safety and tolerability of an ultrarush high-dose sublingual immunotherapy (SLIT) regimen reaching a maintenance dose of 300 index of reactivity within 90 minutes. METHODS: Children and adolescents aged 5 to 17 years with at least a 1-year medical history of allergic rhinitis with or without mild to moderate asthma due to tree pollens (birch, alder, hazel) or grass pollens (cocksfoot, meadow grass, rye grass, sweet vernal grass, timothy) were recruited. Standardized grass and tree pollen allergen extracts were used for ultrarush titration and subsequent coseasonal maintenance. RESULTS: During ultrarush titration, 60 patients (31%) reported 117 predominantly mild and local adverse events, which resolved within 150 minutes. During the maintenance phase, 562 adverse events were reported; the most frequent local events were oral pruritus, burning sensation, lip or tongue swelling, and gastrointestinal symptoms, and the most frequent systemic events were rhinoconjunctivitis and asthma. There was 1 clinically significant asthma event in an 11-year old boy with known asthma in whom SLIT was resumed after an interval of 4 days. CONCLUSION: Ultrarush titration was safe and well tolerated. Pediatric patients with asthma should be carefully monitored and adequately trained to use their rescue medications. PMID- 19476017 TI - Histopathologic changes in two mouse models of asthma. AB - BACKGROUND: No studies to date have compared mouse models of asthma by evaluating airway histopathology. OBJECTIVE: To compare 2 such models by studying chronic histopathologic changes of the airways using light and electron microscopy. METHODS: Twenty-one male BALB/c mice were divided into 3 groups: a nebulization group sensitized via an intraperitoneal injection of 10 microg ovalbumin on days 0 and 14 and exposed to 2.5% aerosolized ovalbumin 3 days a week over the subsequent 8 weeks; an intranasal group sensitized via 2 intraperitoneal injections of 100 microg ovalbumin on days 0 and 14 and administered an intranasal dose of 500 microg ovalbumin on days 14, 27, 28, 29, 47, 61, 73, 74, and 75; and a control group that received nothing. Airway histopathologies were evaluated. RESULTS: Basement membrane, epithelium, and subepithelial smooth muscle layer thicknesses and mast and goblet cell numbers were significantly higher in the nebulization group than in the control group. With the exception of mast cell numbers, these parameters were also significantly higher in the intranasal group than in the control group. On comparing the intranasal and the nebulization group, goblet cell numbers were significantly higher in the former and mast cells in the latter. CONCLUSION: Both models replicated all the structural parameters of asthma except for mast cell numbers in the intranasal group (no significant difference with respect to the control group). Our findings do not provide sufficient evidence that one protocol is superior to the other. Larger studies are needed to compare different asthma protocols. PMID- 19476018 TI - Adverse reactions of prophylactic intravenous immunoglobulin; a 13-year experience with 3004 infusions in Iranian patients with primary immunodeficiency diseases. AB - Intravenous immunoglobulin (IVIG) replacement therapy improves health-related quality of life in patients with a primary immunodeficiency disease, although there have been reports of adverse reactions associated with its regular administration. The study population was composed of 99 patients with primary antibody deficiencies. All the patients were diagnosed with a primary immunodeficiency disease and received at least 4 infusions of IVIG at the Children's Medical Center Hospital, Tehran, Iran over a 13-year period (1995 2007). A total of 3004 infusions were recorded, and 216 (7.2%) of these were associated with adverse reactions in 66 patients. Adverse reactions were classified as mild (172 reactions), moderate (41 reactions), and severe (3 reactions). The rate of adverse reaction varied by diagnosis from 3.35% in patients with X-linked agammaglobulinemia to 17.4% in IgG subclass deficiency. There were no age-related differences in the rates of adverse reactions. Adverse reactions to IVIG infusions are occasionally encountered; therefore, physicians and nurses should be aware of these reactions in order to manage and prevent them. PMID- 19476019 TI - Association analysis of TIM-1 -232G > A and 5383_5397 insertion/deletion polymorphisms with childhood asthma and total serum immunoglobulin E levels in middle China. AB - BACKGROUND: One of the members of the T cell immunoglobulin (Ig) domain and mucin domain (TIM) gene family, TIM-1, located in the chromosome 5q31-33 region, has been associated with the development of T helper (T(H)) 2-biased immune responses and may be selectively expressed in T(H)2 cells. Previous studies have also shown an association between polymorphisms in the TIM-1 gene and asthma or asthma related phenotypes. OBJECTIVE: The aim of the present study was to analyze the association between the TIM-1 polymorphisms -232G > A and 5383_5397 insertion/deletion (ins/del) and susceptibility to asthma in a group of patients from middle China. METHODS: Polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis and PCR-polyacrylamide gel electrophoresis were used to detect -232G > A and 5383_5397 ins/del genotypes in 302 asthmatic children and 206 controls. Serum total IgE was measured by chemiluminescence and specific IgE to common aeroallergens by immunoblot analysis. RESULTS: We found no association between the -232G > A polymorphism and asthma or total serum IgE levels or statistically significant differences between asthma and control subjects in terms of genotype and allele frequency for the 5383_5397 ins/del polymorphism.We did, however, detect a difference in total serum IgE levels for 5383_5397 ins/ins genotypes in individuals with atopic asthma (P < .05) in that they had higher IgE levels than those with del/del and del/ins genotypes. CONCLUSION: Our results suggest that the 5383_5397 ins/ins genotype in the TIM-1 gene is associated with elevated serum total IgE levels, particularly in individuals with atopic asthma. Further studies are needed to confirm such an association. PMID- 19476020 TI - Lettuce-induced anaphylaxis. Identification of the allergen involved. AB - BACKGROUND: Only 2 allergenic proteins have been described in lettuce allergy: a 16-kDa protein (putative profilin) and a lipid transfer protein (LTP) named Lac s 1. OBJECTIVE: Our aim was to identify the allergens involved in the anaphylactic reactions of 2 patients who had eaten lettuce. METHODS: The study was performed by Ig (immunoglobulin)-E immunodetection and immunodetection-inhibition assays. RESULTS: Both patients' sera showed specific IgE binding to a single protein from the crude lettuce extract (apparent molecular weight of 14 kDa). To characterize the allergen detected, the lettuce extract underwent proteolytic digestion and heat treatment and was highly resistant to both. The patients' sera also recognized the major peach allergen Pru p 3 by immunodetection. When the lettuce allergen was incubated with both Pru p 3 from peach peel and recombinant Pru p 3, the immunodetection-inhibition assay indicated that patients were sensitized to the lettuce LTP Lac s 1. CONCLUSIONS: The allergen involved in the lettuce induced anaphylaxis of our patients was the LTP Lac s 1. PMID- 19476021 TI - Recalcitrant nasal polyposis: achievement of total remission following treatment with omalizumab. PMID- 19476022 TI - Benefits of alpine mountain climate of Bavaria in patients with allergic diseases and chronic obstructive pulmonary disease: results from the AURA* study. PMID- 19476023 TI - Allergic contact dermatitis to polyethylene terephthalate mesh. PMID- 19476025 TI - Immediate-type allergic reaction to cefuroxime: cross-reactivity with other cephalosporins, and good tolerance to ceftazidime. PMID- 19476024 TI - An alternative approach to a renal transplant patient who experienced an immediate type systemic reaction due to methylprednisolone sodium succinate. PMID- 19476026 TI - Monosensitization to Blomia tropicalis: is exposure the only factor involved? PMID- 19476027 TI - Professional development: a lifelong investment and journey with curricular mileposts. PMID- 19476028 TI - Health literacy knowledge and experiences of senior baccalaureate nursing students. AB - This study assessed the health literacy knowledge and experiences of senior baccalaureate nursing students enrolled at state universities in Louisiana. A total of 361 nursing students at eight institutions completed the Health Literacy Knowledge and Experience Survey. Results indicated participants were able to identify low socioeconomic groups at high risk for low health literacy, were aware of the consequences associated with low health literacy, and could identify effective interventions used to evaluate patients' understanding of health care teaching. However, knowledge gaps were evident in the following areas: identifying older adults as a high-risk group, screening for health literacy, and assessing guidelines for written health care information. Responses to the Health Literacy Experience scale suggest participants' health literacy experiences were limited regarding conducting health literacy screenings and assessing the reading level, illustrations, and cultural appropriateness of written materials. PMID- 19476029 TI - Tobacco dependence treatment education for baccalaureate nursing students. AB - Tobacco use is the leading cause of preventable disease and death in the United States. Nurses are effective interventionists for tobacco dependence treatment but lack the related education. This quasi-experimental study evaluated the impact of the Rx for Change: Clinician-Assisted Tobacco Cessation curriculum on baccalaureate nursing students' perceived knowledge, confidence, skills, and opinions related to tobacco dependence treatment. Cohort 1 completed a process evaluation to assess acceptability of the pretraining survey and intervention. Cohort 2 completed pretraining and posttraining surveys. A subsample received a 2 hour intervention, whereas other participants received 6 hours of training. Cohort 1 rated the pretraining survey instrument favorably. In cohort 2, the Rx for Change program had a positive impact on perceived knowledge, confidence, skills, and opinions. Outcomes did not differ based on duration of intervention or students' smoking status. Further research related to standardized content for tobacco dependence treatment is indicated. PMID- 19476030 TI - Tuberculosis education for nurse practitioner students: where we are and where we need to go. AB - Tuberculosis (TB) has reemerged as a public health concern. This study tested the reliability and validity of an instrument examining self-efficacy in providing TB care, beliefs about educational preparation, and knowledge about TB among nurse practitioner students from diverse programs. A one-time self-report instrument was distributed during a final clinical course. Rasch analysis was used to assess the instrument's reliability and validity. Most of the 92 respondents were from family nurse practitioner programs and had received TB education via lecture. Students were moderately knowledgeable on TB content and had a moderate level of perceived self-efficacy. They valued TB education as it related to both their current program and their clinical practice. The instrument had excellent reliability (alpha = 0.96 to 0.98), and it appears to be an effective measure to help faculty understand student knowledge and confidence in the care of individuals with TB. PMID- 19476031 TI - Education evolution: a historical perspective of associate degree nursing. AB - Exploring the inception and growth of associate degree nursing education informs our understanding of what led to such explosive growth so that most of the nursing workforce is currently educated at the associate degree level. The success of associate degree nursing programs led to many divisive years in nursing education of differentiation of practice debates that were hardly productive. Work world practices and patient needs are creating pressures on community colleges to join forces with universities to increase the percentage of baccalaureate-educated nurses. Associate degree nursing education continues to evolve to meet the demands of a higher educated nursing workforce. PMID- 19476032 TI - Addressing substance abuse among nursing students: development of a prototype alternative-to-dismissal policy. AB - Substance abuse and dependency are health issues that require effective policies within nursing education. In 2007, the University of Memphis School of Nursing drafted a new substance abuse policy using the American Association of Colleges of Nursing's Policy and Guidelines for Prevention and Management of Substance Abuse in the Nursing Education Community. These guidelines include the assumption that addiction is an illness that can be treated and the philosophy that schools of nursing are committed to assisting students with recovery. The new policy at University of Memphis School of Nursing incorporated prevention, education, identification, evaluation, treatment referral, and reentry guidelines, as well as disciplinary action for students unwilling to undergo rehabilitation. It is hoped this new substance abuse policy will serve as a prototype for other institutions. PMID- 19476033 TI - Starting an accelerated baccalaureate nursing program: challenges and opportunities for creative educational innovations. AB - Accelerated baccalaureate nursing programs provide many benefits to students, faculty, nursing educational institutions, and health care institutions. Students, faculty, and nursing program administrators also face a variety of challenges with accelerated programs. This article reviews what is known about accelerated programs, strategies undertaken during the start-up of a new program to enhance its success, and evaluation of the new program. In addition, implications for future research and nursing education are discussed. PMID- 19476034 TI - An integrative curriculum for accelerated nursing education programs. AB - The number of accelerated baccalaureate and direct-entry master's nursing programs being offered in the United States is increasing. These programs shorten the amount of time to educate entry-level nurses. This article describes one school's curriculum for a direct-entry master's nursing program. A faculty task force developed the curriculum and used the opportunity to change the educational paradigm from traditional pedagogical to a concept student-learning approach. The curriculum design, which integrates nursing content through a conceptual model, and an innovative clinical experience model are described. In addition, the article discusses the successes and challenges of the program encountered during the first 2 years of initiation of the curriculum. PMID- 19476035 TI - A longitudinal analysis of the self-directed learning readiness level of nursing students enrolled in a problem-based curriculum. AB - Self-directed learning is an important outcome of nursing education. Although problem-based learning is believed to facilitate self-directed learning, previous studies have reported conflicting results. This longitudinal survey explored the perceived changes in self-directed learning for 4 years in a baccalaureate nursing education program with an integrated problem-based learning curriculum. Fifty of 59 students (response rate, 85%) completed the Self-Directed Learning Readiness Scale at five different time points: at the beginning of each academic year and at program completion. Scores were significantly lower during the first academic year compared with other years, and fourth-year scores were significantly higher than in previous years. Scores on the three subscales (i.e., self-management, desire for learning, and self-control) increased significantly during the 4 years of the program. These findings support self-directed learning as a maturational process. Implications for nursing faculty and curriculum development are discussed. PMID- 19476037 TI - Web-enhanced modules in client assessment. PMID- 19476038 TI - An update on "The Bomb Medic". PMID- 19476036 TI - The importance of instruction on mass casualty incidents in baccalaureate nursing programs: perceptions of nursing faculty. AB - This study examined whether a relationship exists between mass casualty incident knowledge and perceived importance of incorporating competencies regarding mass casualty incidents into baccalaureate nursing programs by faculty in Louisiana. A total of 285 educators in baccalaureate nursing programs in Louisiana were asked to complete the survey instrument; usable surveys was collected from 166 participants (58%). Results indicated participants had limited training and life experiences regarding mass casualty incidents, as well as limited knowledge of mass casualty incidents. However, participants perceived mass casualty incident instruction as important for inclusion in nursing curricula. There was a positive relationship between self-perceived knowledge of mass casualty incidents and perceived importance of including these competencies into the nursing curriculum. These findings suggest schools of nursing take steps to identify or train a pool of educators who can teach mass casualty incident preparation. PMID- 19476039 TI - Go west, young dentist, Go west! PMID- 19476040 TI - Little roses of Sarajevo. PMID- 19476041 TI - Restoring teeth with prefabricated fiber-reinforced resin posts. AB - The use of fiber-reinforced resin (FRR) posts to restore endodontically treated teeth has gained popularity as an alternative to cast or pre-fabricated metal posts. This may be due to the two important characteristics of fiber posts: (1) their modulus of elasticity, which is similar to that of dentin, and (2) their ability to be adhesively cemented. The following article will discuss these characteristics, clinical indications for FRR posts, as well as increased fracture resistance, adhesion to root dentin, and guidelines for placement. PMID- 19476042 TI - Doing it just right: the 2009 MDA president's interview. PMID- 19476043 TI - What is your diagnosis? Osteonecrosis of the jaw; unknown cause(s). PMID- 19476044 TI - The main chance. PMID- 19476045 TI - 2009 electronic claim requirements for Minnesota dentists. AB - This article explains Minnesota Statute 62J.536, which is a new law requiring all health care providers and payers doing business in Minnesota to use electronic formats for billing, eligibility, and remittance advice. The focus of this article is on dentists and what they must do to be in compliance. PMID- 19476046 TI - What's a dentist to do? You always have a choice. PMID- 19476047 TI - A dark and stormy dentist. PMID- 19476048 TI - From pollinosis to digestive allergy. AB - Pollinosis is defined as the appearance of respiratory symptoms (rhinoconjunctivitis and/or asthma) as a result of the inhalation of pollen to which the individual is sensitized. Pollen allergy becomes all the more relevant on taking into account that it may be responsible for the development of plant food allergy, or may even constitute the direct cause of esophageal, gastric and/or intestinal inflammation in the context of a digestive allergic process. Pollen can act as a source of allergens that induce primary sensitization in the host as a result of inhalation, with secondary allergy to plant foods containing shared allergens via a cross-reactivity mechanism. The observed pattern of plant food allergy depends on the dietary habits of the population in a given geographical setting, and on the pollination found in that setting. Pollinosis may account for the greater or lesser prevalence of allergy to certain plant foods, and for the severity of the associated reactions. Beyond the digestive tract inflammation that may result from allergy to a given food, pollinosis is also intrinsically able to generate a clinically relevant or irrelevant Th2 mediated inflammatory response at digestive level, and may even give rise to eosinophilic esophagitis. Inter-relation with the airway may also extend to the digestive tract as a consequence of the systemic response that characterizes allergic disease. PMID- 19476049 TI - Allergic conjunctivitis and H1 antihistamines. AB - Allergic conjunctivitis is the most common form of ophthalmological allergy. Eye symptoms are one of the main and most frequent reasons for consultation among patients with allergic rhinoconjunctivitis, which in turn is the most common reason for visiting the allergologist, according to the Alergologica 2005 study. Itching is the key symptom of allergic conjunctivitis, and its relief is the principal objective of the broad range of treatment options available. Topical antihistamines with multiple actions (mast cell stabilization, and antiinflammatory and antihistaminic actions) are probably the best treatment option, thanks to their rapid action, safety and convenience of use. However, oral antihistamines (preferentially second generation drugs) can also play an important role, since they are of established efficacy and offer adequate treatment of the nasal symptoms that tend to accompany the ocular manifestations of allergic rhinoconjunctivitis. Models of allergic conjunctivitis are useful for investigational purposes and for advancing our knowledge of allergic reactions. Advances in the study of the physiopathology of ocular allergy allow us to introduce new therapeutic options for the management of such allergic reactions, thanks to the findings derived from models of this kind. The present review provides an update to the published data on allergic conjunctivitis and the current role of both topical and ocular antihistamines in treating the disorder. PMID- 19476050 TI - Molecular diagnosis in allergology: application of the microarray technique. AB - Recombinant and purified allergens are currently available for determining specific IgE targeted to different allergenic components. In this way it is possible to diagnose the sensitization profile of each individual patient. The microarray technique makes it possible to determine specific IgE against multiple allergens simultaneously in one same patient, with a minimum amount of serum, and even allows the determination of IgG and IgM against the same allergens in one same serum sample. Microarray procedures are being developed not only for the determination of antibodies but also for cell activation tests. In addition, microarray technology will help explain cross-reactions, and will facilitate the evaluation of subjects in which skin tests cannot be performed. These techniques will allow a great step forward in the development of immunotherapy specifically targeted to the sensitizations found in each individual patient, yielding especially hypoallergenic forms of great immunogenic capacity, and thus improving the safety and efficacy of immunotherapy. Lastly, microarrays will improve our understanding of the physiopathology of allergic diseases. PMID- 19476051 TI - Genetic aspects of allergic rhinitis. AB - The development of allergic rhinitis entails a complex interaction between genetic predisposition and environmental exposure to different factors, of which the most important is the implicated allergen. There is a clear hereditary component in allergic rhinitis that has been well corroborated by segregation studies and investigations in twins. From the strictly genetic perspective, it is believed that the disease may be the result of the interaction of different genetic alterations, each of which would contribute a small defect. In recent years, considerable attention has focused on the genes that may be implicated in allergic rhinitis. A number of genomic searches have been made, yielding different chromosomal associations--the most repeated being those involving chromosomes 2, 3, 4 and 9. Single-nucleotide polymorphism studies involving genes encoding for molecules implicated in the pathogenesis of allergic rhinitis have also been made. Such molecules comprise chemokines and their receptors, interleukins and their receptors, eosinophil peroxidase and leukotrienes, among others. PMID- 19476052 TI - Allergic rhinitis and school performance. AB - Allergic rhinitis is presently the most common chronic disorder in the pediatric population. It can affect sleep at night and cause daytime sleepiness, with school absenteeism, "presenteeism" or inattention, mood disturbances and psychosocial problems. All this in turn can contribute to reduce school performance. The correct treatment of allergic rhinitis can improve school performance, though the first generation antihistamines have unacceptable central and anticholinergic effects that can actually worsen the situation. The second generation antihistamines constitute the drug treatment of choice for allergic rhinitis in children. Vasoconstrictors should not be used in pediatric patients, due to their unpredictable pharmacokinetics and very narrow therapeutic margin. Intranasal corticoids could improve school performance in some patients, by reducing nose block or congestion, the nocturnal sleep disturbances, and daytime sleepiness. Concrete studies of the impact of chromones, anticholinergic agents, antileukotrienes and immunotherapy upon school performance are lacking. PMID- 19476053 TI - Stress and allergy. AB - In recent years it has been seen that the nervous and immune systems regulate each other reciprocally, thus giving rise to a new field of study known as psychoneuroimmunology. Stress is defined as a general body response to initially threatening external or internal demands, involving the mobilization of physiological and psychological resources to deal with them. In other words, stress is characterized by an imbalance between body demands and the capacity of the body to cope with them. The persistence of such a situation gives rise to chronic stress, which is the subject of the present study, considering its repercussions upon different organs and systems, with special emphasis on the immune system and--within the latter--upon the implications in relation to allergic disease. Activation of the neuroendocrine and sympathetic systems through catecholamine and cortisol secretion exerts an influence upon the immune system, modifying the balance between Th1/Th2 response in favor of Th2 action. It is not possible to affirm that chronic stress is intrinsically able to cause allergy, though the evidence of different studies suggests than in genetically susceptible individuals, such stress may favor the appearance of allergic disease on one hand, and complicate the control of existing allergy on the other. PMID- 19476054 TI - [Neuroimmunology and neurovirology]. PMID- 19476055 TI - [Multiple sclerosis and pregnancy]. AB - Mulltiple sclerosis and pregnancy Multiple sclerosis (MS) is diagnosed between the second and fourth decade. More than 2/3 of patients are women and are often in childbearing age. We may ask two main questions: Which implication of pregnancy on the evolution of MS has to be considered ? Which influence of MS on the pregnancy is expected? In other words could the pregnancy worsen MS and could MS represent specific risks for the pregnancy? PMID- 19476056 TI - [Autoantibodies in neurological diseases: clinical implications]. AB - Autoantibodies are defined as antibodies directed against self antigens, i.e., against a normal antigenic endogenous tissue constituent. They can be the immediate cause of the neurological syndrome or be detected as an epiphenomenon of the pathogenic process. Autoantibodies are often considered useful biomarkers for the improvement of diagnostic accuracy, for the staging of disease progression or for the follow up of a biological response to a therapeutic intervention. The purpose of this article is to review the autoantibodies that are available to investigate immune-mediated neurological conditions. The detection of some of these autoantibodies may help the clinician to establish a definite diagnosis which may further facilitate the therapeutic decision. PMID- 19476057 TI - [Neurobehavioral changes occurring during multiple sclerosis]. AB - Behavioral changes occurring in patients affected by multiple sclerosis (MSI are often neglected by physicians but are actually part of the clinical spectrum of the disease. In addition, they are known to be responsible for a decline in the quality of life of MS patients. Recently, there has been a growing interest to investigate changes in the emotional experience of MS patients and their decision making, showing that the ability to take advantageous decisions was altered in MS. This paper reviews existing data on this topic. PMID- 19476058 TI - [New spectrum of HIV-associated cognitive disorders in the HAART era]. AB - Highly active anti-retroviral therapy (HAART) has almost abolished HIV-related mortality and serious opportunistic diseases; among them, AIDS-related dementia. However, minor forms of cognitive dysfunction, have not disappeared, and even increased in frequency. Ageing of HIV+ patients, insufficient penetration of anti viral drugs into the brain with continuous low-grade viral production and inflammation may play a role. Minor cognitive dysfunction in HIV infection shares some clinical and pathophysiological features with neuro-degenerative diseases, in particular Alzheimers disease. It can thus be postulated that, such in Alzheimer disease, anti-cholinesterase drugs might also be efficacious in AIDS related minor cognitive dysfunction. This hypothesis has not been tested yet however A clinical trial using ravistigmine is starting this spring in patients with HIV-associated cognitive dysfunction in Geneva and Lausanne. PMID- 19476059 TI - [Neuropathy associated with monoclonal gammopathy (dysglobulinemia)]. AB - Neurological complications of monoclonal gammopathy, or dysglobulinemia, are typically affecting the peripheral nerve. The clinical course is often chronic and progressive and requires a precise diagnosis of the type of plasma cell disorder associated with the neuropathy, to investigate other organs manifestations and to assess the presence of specific markers. These steps are required to initiate an appropriate therapy that may include chemotherapy, immunosuppressive or immunomodulatory treatment. PMID- 19476060 TI - [Viral encephalitis: update]. AB - Suspicion of viral encephalitis should always be considered as a medical emergency and the prognosis depend on both the immune status of the host and the virulence of the virus. Among them, the herpes simplex virus is by far the most important one since it can be associated with severe encephalitis in immunocompetent host, and because a good response to acyclovir can be expected when rapidly initiated. Nevertheless, confirmation of the diagnosis requires exclusion of both metabolic or toxic encephalopathy and inflammatory encephalitis of non-infectious origin. In addition, other germs than viruses can mimic viral encephalitis and must be taken into consideration. The purpose of this review is to update the investigation that should be performed in clinical practice for any patient with suspicion of acute viral encephalitis. PMID- 19476061 TI - [Is hardware removal a necessity?]. AB - Hardware removal should be decided only after careful examination of the medical and economic implications. Current literature fails to offer systematic guidelines. Infected hardware, non-union after surgery or obvious mechanical problems are straightforward indications for implant removal. However, when motivated by pain alone, the procedure can have disappointing results, and patients' expectations should be consequently moderated. Protection against toxicity, allergy, carcinogenesis or possible implant failure should not prompt systematic removal. Hardware removal in children should be considered separately, since metallic implants can interfere with normal growth patterns. Overall, implant removal should not be considered a routine procedure, and indications for surgery should reflect the thorough examination of the risks and the benefits. PMID- 19476062 TI - [Sleep apnea: post CPAP residual sleepiness]. PMID- 19476063 TI - [French subtlety in distress]. PMID- 19476064 TI - [The American policy of taxing sodas]. PMID- 19476066 TI - Beyond the realities of current practice: preparing students to provide safe and effective care. PMID- 19476065 TI - [Ethics, its detractors, and its strange attractors]. PMID- 19476067 TI - Dreams for the future for clinical simulation. PMID- 19476068 TI - High-fidelity simulation: factors correlated with nursing student satisfaction and self-confidence. AB - While available research suggests positive outcomes when using high-fidelity simulation in nursing education, little is known about factors associated with these outcomes. This descriptive, correlational study examined the effects of a simulation experience on two outcomes (student satisfaction and self-confidence) as well as factors correlating with these outcomes. This was accomplished by both descriptive statistical analysis (mean and standard deviation) in addition to correlational statistical analysis using bivariate statistics (Spearman's rho) and multiple linear regression. Results indicate that design characteristics, especially clear objectives and an appropriately challenging problem to solve, were significantly correlated with student satisfaction and self-confidence. PMID- 19476069 TI - Outcomes of clinical simulation for novice nursing students: communication, confidence, clinical judgment. AB - The use of clinical simulation in nursing education provides many opportunities for students to learn and apply theoretical principles of nursing care in a safe environment. The purpose of this study was to evaluate simulated clinical experiences as a teaching/learning method to increase the self-efficacy of nursing students during their initial clinical course in a prelicensure program. An integrated, quasi-experimental, repeated measures design was used. A sample of 112 students completed surveys, indicating their confidence in various skills necessary for postpartum and newborn nursing, both before and after the simulation experience. Results indicated that students experienced a significant increase in overall self-efficacy (p < .01). Students also experienced an increase in confidence in assessing vital signs (p < .01), breasts (p < .01), the fundus (p < .001), and lochia (p < .001), and in providing patient education (p < .001). Three themes that emerged in the qualitative results were communication, confidence, and clinical judgment. PMID- 19476070 TI - The case for group planning in human patient simulation. AB - This evaluation research focused on ways to improve the simulation learning experiences of prelicensure nursing students participating in a high-acuity nursing course. Based on the findings of a paper-and-pen midterm formative evaluation, focus groups were held to learn more about student attitudes regarding their simulation experience.Two themes emerged: (1) students felt unfairly "singled out" during simulation and perceived that their apprehension interfered with their learning, and (2) collaborative learning could be a potential strategy for dealing with feeling singled out. In response to these concerns, faculty included a group-planning experience for each remaining simulation. Students immediately reported that their anxiety lessened and that they learned more from their simulation experiences. In their final evaluations, students identified group-planning sessions as the most helpful component of the simulation experience. These findings suggest that group care planning may be an important simulation design component. PMID- 19476071 TI - Simulation as a means to foster collaborative interdisciplinary education. AB - The purpose of this study was multifaceted: to initiate an interdisciplinary collaborative relationship between nursing and medical students; to determine the usefulness of an interdisciplinary approach using simulations as an educational strategy; and to analyze students' perceptions of collaboration. A pre/posttest design was used to assess students' perceptions of interdisciplinary collaboration with a mock code experience using a high-fidelity simulator. Open ended questions provided another perspective of interdisciplinary collaboration. A convenience sample of fourth-year nursing students and third-year medical students from a large urban university participated in the study. Statistically significant differences (p < 0.05) were seen in medical students' posttest scores for two factors, collaboration and nursing autonomy. The narrative responses revealed that nursing students' perceptions of the nurse-physician relationship became more collaborative after the simulation experience. Both medical and nursing students described the experience as one that should be continued. PMID- 19476072 TI - Learning advanced cardiac life support: a comparison study of the effects of low- and high-fidelity simulation. AB - To increase cardiopulmonary arrest survival, the American Heart Association developed basic and advanced cardiac life support (ACLS) courses that expose participants to realistic learning situations. This experimental study compared results of two ACLS classes on measures of knowledge (content exam) and resuscitation skills (performance exam). Both the control and experimental groups consisted of physicians, nurses, emergency medical technicians, respiratory therapists, and advanced health care providers. The control group used low fidelity simulation (LFS); the experimental group was exposed to enhanced realism via high-fidelity simulation (HFS). The findings showed a positive correlation between enhanced practice and learning but no significant correlation between posttest and skills test scores for the LFS and HFS groups. The HFS group did score higher on both cognitive and behavioral tests, but the difference was not statistically significant. Participants from both groups indicated satisfaction with their forms of simulation experience and course design. In addition, participants' self-confidence to care for a victim of cardiopulmonary arrest was increased after completing their course; profession and work experience had no effect on responses. The largest difference noted was in verbal responses to course satisfaction. The experimental group stated that learning using HFS was enjoyable and adamantly recommended that ACLS should only be taught using HFS. Further study is required to assess if practicing beyond the course enhances short- and long-term retention of ACLS techniques. PMID- 19476073 TI - Student satisfaction with high-fidelity simulation: does it correlate with learning styles? AB - The purpose of this study was to explore how learning styles correlate with student satisfacation when high-fidelity human simulation is used in a baccalaureate nursing program. Seventy-eight undergraduate students enrolled in an advanced medical-surgical course completed the Student Satisfaction and Self Confidence in Learning scale after participating in an experiental learning lab activity that included high-fidelity human simulation-enhanced cardiac case scenarios. Data were then correlated with learning styles identified by a nurse entrance test. Analyses of the data revealed positive relationships between the social and solitary learning styles and student satisfaction with simulation. PMID- 19476074 TI - A collaborative project to apply and evaluate the clinical judgment model through simulation. AB - As use of simulations increases in nursing education, nurse educators are challenged to evaluate students' clinical judgment skills. The purpose of this article is to describe faculty development in the use of the Lasater Clinical Judgment Rubric (LCJR); faculty application of LCJR in evaluating students' clinical judgment skills during a simulation scenario; and faculty and students' perception transference from the simulation to the clinical setting.Tanner's Clinical Judgment Model was used in an assigned adult health simulation. Quantitative and qualitative data were collected from faculty and student evaluations and students' reflective statements. Findings support the importance of simulation's contribution to clinical judgment development. However, more work remains to improve the integration of clinical judgment and use of a conceptual framework and evidence-based rubric. For long-term change, both faculty and students need ongoing practice and encouragement in applying the clinical judgment framework to clinical and simulation experiences. For application of the model, a recommendation is to incorporate the clinical judgment language into course syllabi, course assignments, and evaluations. PMID- 19476075 TI - Nursing students' self-assessment of their simulation experiences. AB - This article describes a self-evaluation and feedback strategy used by nursing students and simulation faculty in a junior-level adult acute care course. Simulations are developed and implemented with the intention of furthering students' clinical judgment skills. A clinical judgment rubric, based on the Tanner Model of Clinical Judgment, is used as a self-assessment tool. The rubric describes the development of clinical judgment over four levels and is scored by students as they reflect on their practice. In addition to using the rubric's descriptors to rate themselves (Beginning, Developing, Accomplished, and Exemplary), the students apply an evidence-based process, citing simulation examples of their clinical thinking as support for their ratings. Simulation faculty respond to the postings, affirming students' observations or helping them experience a different perspective, and offer help to move toward the next stage of clinical judgment development. The postings offer clinical faculty insight into clinical judgment processes observed in the practicum settings. PMID- 19476077 TI - Using high-fidelity simulation to educate nursing students about end-of-life care. AB - Despite some technical limitations, it is possible to give students a wide range of experiences related to pre- and postmortem care using high-fidelity simulation in a clinical skills lab. Simulations incorporating role play provide important opportunities for students to explore their own ideas about death and caring for patients who are dying. This article reports on the experience of caring for a simulated patient who dies during the scenario and interacting with a family member represented by a standardized actor. Selected educational models are described that provide guidance in developing evidence-based and patient-centered care simulations. A specific, author-developed conceptual model is used to guide development of specific learning activities; the "Silver Hour" represents the 30 minutes prior to the death and immediately following the death. Care of the imminently dying patient, in any setting, can be conceptualized using this model. Specifically, the model encourages students to explore care for the patient as treatment is withdrawn and death is pronounced and to focus on care for families in managing transitions before and after death. PMID- 19476076 TI - The essentials of debriefing in simulation learning: a concept analysis. AB - Debriefing is essential element of simulation; however, practices vary greatly. Common elements include critique, correction, and evaluation of student performance and discussion of the experience. Learning occurs in simulation through contextual task training and repetition, but significant learning occurs when deep insight is made explicit through reflection during debriefing. The value of the student's learning is in the student's ability to engage in reflection that translates into actionable knowledge. Facilitating debriefing emphasizing reflection is an essential competency, yet little research and resources are available to guide best practices in debriefing. This article analyzes the concept of debriefing and identifies essential components. Examples that demonstrate defining attributes of debriefing are included. This work supports the identification of best practices and future research agendas to enable nurse educators to master the knowledge and strategies needed to provide students with significant learning during simulation. PMID- 19476079 TI - Creative clinical solutions: aligning simulation with authentic clinical experiences. PMID- 19476078 TI - Creating simulation communities of practice: an international perspective. AB - A three-year National League for Nursing grant aimed at faculty development in the use of simulation as a teaching-learning strategy to promote and evaluate student learning outcomes was funded in 2007 by the Laerdal Medical Corporation. The focus of the faculty development project was the creation of nine web-based courses written by nine United States authors with the assistance of eight contributing partners from seven different countries. The process is described from the view of the international participants who worked together with the US experts.The significance of the work, the process, the challenges and barriers, and the benefits and rewards of the work are described. Recommendations for working on a multisite, international collaborative project are also discussed. PMID- 19476080 TI - Nursing education 2.0: a second look at Second Life. PMID- 19476081 TI - Overview of embryological development of the canine oral cavity. PMID- 19476082 TI - Dimensions of diastemata and associated periodontal food pockets in donkey cheek teeth. AB - Equine cheek teeth (CT) diastemata often cause deep periodontal food pocketing and are therefore regarded as a painful dental disorder of equidae. However there appears to be no information available on the size or shape of these diastemata. This post mortem study examined 16 donkey skulls (mean age = 32-years) containing 45 CT diastemata to define the anatomical shape and dimensions of these diastemata, and of the associated periodontal food pockets that occur with this disorder. Diastemata were found to more commonly involve mandibular (56.0%) compared with maxillary CT (44.0%), and 71.0% of these diastemata had adjacent intercurrent dental disorders that may have predisposed donkeys to the diastemata. The median widths of all diastemata were 2.0-mm at the occlusal surface and 3.1-mm at the gingival margin, with no diferences in widths between the lateral or medial aspects of diastemata. Diastemata were defined as open (60.00%) or valve (40.00%) based on their gross appearance. This classification was confirmed to be accurate by measurements that showed valve diastemata to have an occlusal to gingival width ratio of 0.4, in contrast to open diastemata where this ratio was 1.07. Food was impacted in 89.0% of diastemata, but all diastemata had adjacent periodontal disease. Periodontal food pocketing was present adjacent to 76.0% of diastemata, more commonly on the lateral aspect (73.0% prevalence; mean pocket depth = 4.1-mm) than the medial aspect (47.0% prevalence; mean pocket depth = 2.4-mm). The depth of periodontal pockets of diastemata was not associated with the height of the erupted crowns of adjacent CT. PMID- 19476083 TI - Oral examination and radiographic evaluation of the dentition in wild cats from Namibia. AB - Feline tooth resorption has been widely reported in domestic cats and sporadically described in other felidae. The goal of the present study was to determine the prevalence of tooth resorption and to report other dental problems in a population of wild felidae. Observations of dental disorders and anomalies were made in skulls from 73 wild felidae (cheetahs, leopards, caracals, African wildcats, and lions) originating from Namibia. In addition, radiographs were taken in 43 cases to determine signs of bone and root pathology. Radiographs showed varying stages of tooth resorption in 16.0% of the specimens. Other dental anomalies found included fused teeth, supernumerary roots, or missing teeth. The prevalence of dental resorption in wild felidae was lower than reported in the domestic cat. PMID- 19476084 TI - Application of the gingival contour plaque index: six-month plaque and gingivitis study. AB - The Gingival Contour Plaque Index (GCPI) is a recently introduced and validated method of measuring plaque accumulation in dogs. It focuses on plaque accumulated along the gingival margin. Plaque accumulation in this area leads to gingival inflammation and, potentially, periodontitis. A 6-month plaque and gingivitis study was conducted to demonstrate the clinical research application of the GCPI, and to ensure that documented quantification of plaque-reducing efficacy could be related to a reduction in gingivitis. Advantages of the GCPI method are the ability to quantify plaque accumulation in an awake dog with fewer research personnel and more efficient time usage. PMID- 19476085 TI - Resection of mast cell tumor of the lip in a dog. AB - A 10-year-old Boston terrier dog was presented for treatment of a 2-cm mast cell tumor of the left upper lip and nasal planum immediately adjacent to the philtrum and ventral to the nares. CO2 laser was used for resection of the lesion. Wound reconstruction was performed using bilateral labial advancement flaps. PMID- 19476086 TI - Restorative dental treatment of a canine tooth in a Bornean orang utan. PMID- 19476087 TI - Dental homecare: teaching your clients to care for their pet's teeth. PMID- 19476088 TI - Interarcade bonding for non-invasive mandibular fracture repair. PMID- 19476090 TI - Molar incisor hypomineralization. AB - Enamel defects are common alterations that can occur in both the primary or permanent dentition. A range of etiological factors related to this pathology can be found in the literature. Molar Incisor Hypomineralization (MIH) is a kind of enamel defect alteration that requires complex treatment solutions, and for this reason, it is of great clinical interest for dental practice. This article describes the management of a clinical case of MIH in a 7-year-old child. The different treatment options depending on the extension of the defect, the degree of tooth eruption and the hygiene and diet habits of the patient are also discussed. PMID- 19476089 TI - Clinical efficacy of 5% sodium hypochlorite for removal of stains caused by dental fluorosis. AB - The objective of this study was to evaluate the clinical efficacy of 5% sodium hypochlorite solution for removal of stains caused by dental fluorosis in young patients. A clinical trial involved 33 patients with diffuse opacities on the enamel surfaces of maxillary incisors due to effects of dental fluorosis. The protocol of treatment 3 steps: (1) cleaning and enamel etching with 37% phosphoric acid in order to eliminate the layer that covers the fluorotic enamel surface and allow better penetration of the bleaching agent, (2) application of 5% sodium hypochlorite to remove stains caused by organic material, and (3) filling the opened micro-cavities with a light-cured, composite surface sealant to prevent restaining. The whiteness of the enamel lesions before and after treatment were expressed in L*, a*, and b* color space measurements using a Minolta Chroma Meter CR300. Analysis of parameters of [symbol:see text]E (L*, a*, b*) showed that changes were observed in the L* (brightness) and a* (redness), which paralleled the [symbol: see text]E differences. There was no significant difference in the b* (yellow) parameter. The technique described in this study appears to have advantages over other methods for improving the appearance of fluorotic lesions. It is simple, low cost, non invasive so the enamel keeps its structure, relatively rapid, and safe; it requires no special materials, and it can be used with safety on young permanent teeth. PMID- 19476091 TI - Influence of local factors on cementoenamel junction-alveolar bone crest distance in primary dentition. AB - OBJECTIVE: This study illustrated the influence of local factors (dental biofilm, gingival bleeding, probing depth, proximal contact and proximal caries/inadequate restorations) on the cementoenamel junction (CEJ)-alveolar bone crest (ABC) distance in primary canines and molars of healthy children with complete primary dentition. STUDY DESIGN: Two hundred and four patients have been examined clinically with regard to biofilm's presence, gingival status, probing depth, proximal contact and dental condition (carious lesions/restorations). Two bitewings of each patient were also taken. Eight dental surfaces (second molars mesial, first molars mesial and distal, and canines distal) could be analyzed per bitewing and the CEJ-ABC distance was measured using a digimatic caliper. Statistical analyses were controlled by dental arch, tooth type and surface. Mann Whitney test was used to verify the association between CEJ-ABC distance and local factors. RESULTS: After stratifying the data according to those influencing factors, the only local factor associated with increased CEJ-ABC distances in most of the different analyzed dental surfaces was the increased probing depth (> 2mm), although only two dental surfaces showed statistical significance (p < 0.01). CONCLUSION: Among the analyzed local factors, increased probing depth was the only factor that proved to be relevant in children's alveolar bone loss screening. PMID- 19476092 TI - Cleft lip and palate: association with other congenital malformations. AB - Orofacial clefts are frequently associated with other congenital malformations. Studies vary in incidence and types of anomalies. OBJECTIVE: To evaluate associated malformations in orofacial cleft patients at a major research hospital. STUDY DESIGN: Medical records of 1127 patients, in the Cleft Palate/Craniofacial Clinic, Boys Town National Research Hospital, from January 1980 through February 2000 were reviewed. Patients were divided into two categories: 1) cleft palate only (CP), and 2) cleft lip, with or without cleft palate (CL +/- P). Further categorization included location and type, if any, of other congenital malformations. RESULTS: 47.2% of patients had CP and 52.8% had CL +/- P. 32.2% of all cleft patients had associated congenital malformations. The orofacial region was the most common site, followed by cardiovascular central nervous, and skeletal systems. Congenital malformations were more common in CP (38.7%), than CL +/- P (26.4%). Of malformations diagnosed, 63.1% were chromosomal/syndromic anomalies while 36.9% were non-chromosomal/syndromic. CONCLUSIONS: Recognition of the spectrum of congenital malformations, associated with orofacial clefting, is essential for further diagnostic testing and in some cases genetic counseling. PMID- 19476093 TI - Developmental anomalies of permanent lateral incisors in young patients. AB - OBJECTIVE: To elucidate the prevalence of developmental anomalies of permanent lateral incisors among young patients in Japan. STUDY DEIGN: A total of 1375 patients were observed between 1990 and 2008 at the Department of Pediatric Dentistry in the Kyushu Dental College Hospital and four private pediatric dental clinics in Kitakyushu City. Panoramic and periapical radiographs were examined for all those patients aged 5 to 19 years. RESULTS: The prevalence of agenesis of the lateral incisors was 7.3% (100 patients), with more girls than boys being affected. The prevalence rates of absent upper and lower lateral incisors were 2.7 and 4.8% (34 and 63 patients), respectively. Nine (0.7%) of the total patients had microdontia. Eruption disturbance was present in five patients (0.4%). Two of five patients presented with a disturbed eruption owing to an odontoma or a supernumerary tooth. CONCLUSION: In our study, the prevalence of agenesis of the lateral incisors was higher in Japanese children than in other populations, and eruption disturbance occurred less frequently than agenesis and microdontia. Nevertheless, the early differential diagnosis of an eruption disturbance is important in order to begin appropriate treatment at the optimal time. PMID- 19476094 TI - In vitro toxicity of MTA compared with other primary teeth pulpotomy agents. AB - OBJECTIVE: The main goal of this work is to compare the In vitro toxicity of MTA with other primary teeth pulpotomy agents. STUDY DESIGN: The In vitro toxicity of MTA, calcium hydroxide, ferric sulphate solution, diluted formocresol and Buckley's formocresol were tested using MTT and Neutral Red Uptake cell viability assays. The results for MTA were compared to those obtained for the other substances using ANOVA and Tukey statistical tests (p < 0.05). RESULTS: MTA had the lower in vitro toxicity and Buckley's formocresol, the higher, with statically significant difference. CONCLUSION: Among the primary teeth pulpotomy agents tested, MTA showed the lower In vitro toxicity, standing as the most promising substitute to formocresol. PMID- 19476095 TI - Ultramorphological characterization of the resin dentin interface--an in vitro analysis of nanoleakage patterns of dentin adhesives. AB - AIM AND DESIGN: The requirements of an effective dentin adhesive system include the ability to thoroughly infiltrate the collagen network and partially demineralized zone, to encapsulate the collagen and hydroxyapatite crystallites, to produce a well polymerized durable hybrid layer with high bond strengths. Microleak-age and marginal percolation are the most detrimental factors thwarting the success of any restoration. However the presence of leakage pathways, called nanoleakage have been observed in the hybrid layer, even in the absence of microleakage. The nanoleakage patterns of four dentin adhesives (Prime & Bond NT, AdheSE, Clearfil S3 bond and Fuji Bond LC) was compared using Scanning electron microscopy and Energy Dispersive Spectroscopy, by the silver nitrate penetration method. RESULTS AND CONCLUSION: The results indicated that etch and rinse adhesives showed the maximum nanoleakage followed by the self etch systems. The glass ionomer based bonding agents showed the least nanoleakage. It is extremely important to take nanoleakage as a consideration while choosing dentin adhesives, to ensure success of the restoration. PMID- 19476096 TI - Total antioxidant capacity of saliva and its relation with early childhood caries and rampant caries. AB - Dental caries is an infectious and communicable disease and multiple factors influence the initiation and progression of the disease. Recently it has been claimed that oxidative stress may play an important role in the onset and the development of several inflammatory oral pathologies and dental caries may also be included. Saliva could constitute a first line of defense against free radical mediated oxidative stress. This is the reason why antioxidant capacity of saliva has led to increasing interest and hence the need for this study. The antioxidant capacity of saliva was investigated in 100 children who were divided into four groups. Two of which comprised the study and control groups of children with ECC (below 71 months of age) and the other two groups comprised of the study and control groups of the children with rampant caries [(RC) (6-12 yrs)]. Unstimulated saliva samples were collected from all the groups. Total antioxidant capacity of saliva was evaluated by spectrophotometric assay. The results indicated that the total antioxidant capacity (TAC) of saliva increased in children with caries. TAC also increased with the age of the children. PMID- 19476097 TI - Biofilm formation by Candida species on silicone surfaces and latex pacifier nipples: an in vitro study. AB - The present study assessed the growth and development of biofilm formation by isolates of C. albicans, C. glabrata and C. parapsilosis on silicone and latex pacifier nipples. The silicone and latex surfaces were evaluated by scanning electronic microscopy (SEM). The plastic component of the nipple also seems to be an important factor regarding the biofilm formation by Candida spp. The biofilm growth was measured using the MTT reduction reaction. C. albicans was found to have a slightly greater capacity of forming biofilm compared to the other Candida species. Analysis of the pattern of biofilm development by C. albicans, C. glabrata and C. parapsilosis on latex and silicon pacifier shields showed an increased biofilm formation regarding the latter substrate. Silicone was shown to be more resistant to fungal colonization, particularly in the case of C. parapsilosis, despite the lack of any statistically significant differences (P > 0.05). In addition, silicone has a smoother surface compared to latex, whose surface was found to be rugose and irregular. PMID- 19476098 TI - Relationship between severe early childhood caries, mother's oral health and mutans streptococci in a low-income group: changes from 1996 to 2007. AB - The relationship between dental caries and mutans streptococci (ms) in children and their mothers is a key factor in the prevention of early childhood caries. Changes in early childhood caries over time in Mexican children have not been well documented. OBJECTIVE: To compare the dental caries indices and presence of ms in 3- to 5-year-old children and their mothers in two surveys, the first one carried out in 1996 and the second one in 2007. STUDY DESIGN: Cross-sectional study. RESULTS: The first survey included 102 mother-child dyads and the second 103. Dental caries index dmfs was 7.17 (+/- 10.9) and 4.58 (+/- 7.1) in the first and second survey, respectively (p < 0.05). Ms levels were higher in 1996 than in 2007 (p < 0.001). The prevalence of Severe Early Childhood Caries (SECC) was 42.2% and 34.95% in first and second surveys, respectively, (p > 0.05). Children with SECC showed higher counts of ms than children without this condition. A high caries index in mothers was associated with higher caries experience in their children. CONCLUSION: The compassions of the surveys indicated a decline in dental caries indices over an 11-year period. High caries experience in the mother had a negative impact on the oral condition of the child. PMID- 19476099 TI - Characteristics, clinical features and treatment of supernumerary teeth. AB - AIMS: To determine the characteristics, clinical features and treatment of supernumerary teeth in a general district hospital in the North of Jordan. DESIGN: This retrospective study was conducted at Prince Rashid Al-Hassan Hospital in Irbid. The medical records of 139 patients who were diagnosed to have supernumerary teeth during the period April 1993 - June 2007 were reviewed. Clinical data on the location, number eruption status, stages of development, and the types of supernumerary teeth were recorded, along with information on demographics, treatment, associated systemic syndromes, effects on adjacent teeth, and treatment. RESULTS: The male to female ratio was 2.2:1. Of the 186 supernumerary teeth investigated (65.0%) were conical, (23.7%) supplemental, (10.8%) tuberculate and (0.5%) odontoma. Two-thirds of the supernumeraries were erupted. Of this sample (21.6%) patients had multiple supernumerary teeth. The most frequent location was at the premaxilla level. The most common effect on adjacent teeth was delayed eruption (23.1%). Simple and surgical extractions of supernumerary teeth were done for (81.7%) of the cases and orthodontic treatment was needed in (74.1%) of patients. CONCLUSION: Supernumerary teeth are an uncommon dental entity. An early diagnosis prevents or reduces the risk of complications and when combined with an earlier removal has a better prognosis. PMID- 19476100 TI - Post-traumatic epidermoid inclusion cyst in the chin region. AB - Epidermoid cysts of traumatic origin are found mainly on palms, fingers and soles. They are believed to originate through implantation of epithelium by either surgical or accidental trauma into deeper mesenchymal tissue. A case of traumatic epidermoid inclusion cyst of the chin region is described. PMID- 19476101 TI - Cartilage choristoma (soft tissue chondroma): a rare presentation in the lower lip. AB - Cartilage choristoma (soft tissue chondroma) is an ectopic cartilaginous tissue that is rarely found in oral mucosa. Awareness of such disease entity will guide proper diagnosis and treatment. A case of cartilage choristoma occurring in the lower lip of an 8-year-old child is reported. Potential pathogenetic mechanism and the histologic features of this unusual condition are further discussed. PMID- 19476102 TI - Systemic lupus erythematosus presenting with oral mucosal lesions--a case report. AB - Systemic Lupus Erythematosus (SLE) is an autoimmune rheumatic disease, principally affecting women during child bearing years and is characterized by the presence of auto antibodies against a variety of auto antigens such as double stranded DNA, intracellular ribonuclear proteins and membrane phospholipids. The presentation of lupus erythematosus ranges from a skin rash unaccompanied by extracutaneous stigmata to a rapidly progressive lethal multiorgan disease. A wide spectrum of oral mucosal lesions is found in the cutaneous and systemic forms of lupus erythematosus. We report a 11-year-old female child with classical features of Systemic Lupus Erythematosus associated with oral mucosal lesions. PMID- 19476104 TI - An analysis of the first dental visits in a Federally Qualified Health Center in a socio economically deprived area. AB - Dental caries is the single most common chronic disease affecting children in the USA. Approximately 20-25% children are affected. This not only has serious implications for a child's long-term health and well being but also has serious financial implications. The American Academy of Pediatric Dentistry advocates early intervention with the first dental visit by 12 months of age. OBJECTIVE: The aim of this study was to determine the first dental visit for children living in a socio economically deprived area in Connecticut. This study was conducted at a Federally Qualified Health Center in Connecticut. STUDY DESIGN: Data was collected prospectively on the children between January to December 2004. RESULTS: We found that the mean age for the first visit was 4 years. The recommendation is that community health programs should emphasize the importance of preventive dental care by assuring the first dental visit be by age 1 year. PMID- 19476103 TI - The influence of an oral health education program provided in a community dental clinic on the prevalence of caries among 12-14 year-old children. AB - OBJECTIVES: To evaluate the effectiveness of an oral health education program when given in a public dental clinic, by assessing caries and restorations. METHODS: This was done by assessing changes in caries prevalence in the mouth of children aged 12 to 14 year- old. Data was obtained from files of patients treated in the Dental Volunteers for Israel (DVI) clinic in Jerusalem. Children must prove understanding and also application of what they learned in the educational program in order to receive restorative dental treatment. RESULTS: 280 children were included in the intervention group. The control group constituted 173 children who had never had any restorative treatment in the DVI clinic. The extent of caries surfaces differed greatly between the intervention and the control groups. 35.2% of the control group, and as many as 64% of the intervention group had low caries (DMFS < 3). The situation is reversed when comparing the difference in the restored teeth surfaces between the two groups- 56.6% of the control group had no restorations and 66.2% of the children in the intervention group had treated teeth. DMFS scores reveal fewer differences between the two groups. The mean carious surface was 1.8 times greater in the control group, and the restored surfaces were 2.1 times greater for the intervention children. Nevertheless when comparing DMFS means between control and intervention groups t-test result shows no statistical significant difference for the slightly lower DMFS levels in the intervention group. CONCLUSIONS: This study shows that even a comprehensive preventive program given by professional personnel, followed by free dental treatment, is not enough to improve dental health status for children from a lower socioeconomic class. Still, a consideration of the ethical responsibility of the profession to educate children about oral diseases and their prevention should be carried out, irrespective of the implementation of the knowledge. PMID- 19476105 TI - Risk assessment in patients with heart valve disease facing non-cardiac surgery. AB - Cardiac-related perioperative complications are well-known in general practice. The role of echocardiography in preoperative risk assessment before non-cardiac surgery remains unclear though. In this article we discuss recently published guidelines, articles and opinions in the domain of preoperative risk assessment of patients with valvular heart disease undergoing non-cardiac surgery. We created a risk stratification model that can be used in daily practice. This model may increase our awareness of the risks associated with heart valve disease in the perioperative period. PMID- 19476106 TI - The complexity of platelet metabolism and its contribution to atherothrombosis. AB - Platelet functions are multiple, complex and not limited to haemostasis. In fact, platelets play a relevant role in vascular inflammation and atherosclerosis (ATS). In the presence of vascular lesions or inflammation, endothelial denudation or activation triggers mechanisms that render the circulating platelets adhesive for the vascular wall. Endothelial lesions expose subendothelial matrix components, such as collagen, von Willebrand factor, fibronectin and other adhesive proteins. Platelet adhesion depends on the interaction between these components and platelet receptors (mainly glycoprotein (GP) VI and GPlb-IX-V). Adhesion triggers the platelet release of inflammatory and mitogenic substances that alter the thromboresistant endothelial surface, enhance the chemoattraction of leukocytes, stimulate smooth muscle cell proliferation and contribute to matrix degradation. Finally, GPIIb-IIIa receptors are activated, leading to firm platelet aggregation and thrombus formation. Platelets participate in the formation of mural thrombi in the late stages of atherosclerotic disease, but also adhere to endothelial cells during the earlier stages of atherosclerotic plaque development. Moreover, platelets exert important functions in modulating inflammatory and immune processes. An improved comprehension of the complex platelet pathophysiology could suggest new therapeutic strategies to reduce the impact of atherosclerotic disease. PMID- 19476107 TI - Effect of atrial fibrillation ablation on left atrial contractile function in patients with paroxysmal atrial fibrillation and a relatively well preserved atrial function. AB - OBJECTIVES: There are inconsistent findings regarding the impact of ablation for atrial fibrillation (AF) on left atrial (LA) contractile function. We investigated the ablation effect on LA function in patients with paroxysmal AF. METHODS: Two hundred eighty-nine patients (mean age 56 +/- 9 years) underwent catheter ablation for paroxysmal AF. Transthoracic (TTE) and transoesophageal echocardiography (TEE) were performed at baseline and at 6 and 12 months after ablation for assessment of LA diameter, left atrial appendage emptying velocity (LAAEV), and A-wave peak velocity. RESULTS: LA function before ablation was relatively well preserved (LAAEV 54 +/- 19 cm/s, A-wave 59 +/- 23 cm/s). During follow-up, there was no significant change of LAAEV: from 54 +/- 19 cm/s at baseline to 54 +/- 18 at 6 months and 52 +/- 20 cm/s at 12 months (P = ns).The LA diameter at baseline was 4.2 +/- 0.6 cm and showed no significant change at 6 and 12 months (4.1 +/- 0.6 and 4.1 +/- 0.5 cm, P = ns). There was also no change of the A-wave (59 +/- 23 cm/s before ablation, 59 +/- 27 cm/s at 6 months and 53 +/- 12 cm/s at 12 months, P = ns). CONCLUSIONS: In patients with paroxysmal AF and relatively well preserved LA function, AF ablation leads to no significant deterioration of atrial function. PMID- 19476108 TI - Does preoperative degree of aortic insufficiency influence early and midterm results of sparing surgery? AB - OBJECTIVE: Aortic valve-sparing operations have shown excellent results in patients with aortic root and or ascending aorta aneurysm. Aortic valve regurgitation is frequently detected in these patients as a result of significant dilation of the aortic root.The aim of this study was to assess the impact of preoperative aortic incompetence degree on the early and midterm outcomes of sparing surgery. METHODS: From September 2001 to July 2006, 84 patients with aortic root aneurysm underwent aortic valve-sparing surgery according to the reimplantation technique. Depending on preoperative grade of aortic insufficiency (AI), two groups were identified: 31 patients (study group, SG) with AI grade III IV and 53 (control group, CG) with AI grade II or less. The Gelweave Valsalva prosthesis was used in 76 patients (90.5%). Intraoperative, perioperative variables and outcomes at follow-up were retrospectively compared between the groups. RESULTS: Patient demographics and types of operations were comparable between groups. Early mortality rates were almost identical in both groups (3.2% SG vs. 5.7% CG; P = 0.961); at follow-up (FU), no patient died in both groups. Grade III-IV AI was similar in both groups early postoperatively (6.4% SG vs. 3.8% CG; P = 0.981) and during follow-up (13.3% vs. 8%; P = 0.755). Reoperaton rate for AI was 3.3% in SG vs. 6% in CG (P = 0.980). CONCLUSIONS: Preoperative degree of aortic regurgitation does not impair the outcomes of the valve-sparing operation which seem to depend on more factors. Early results were affected by the learning curve but midterm outcomes showed a progressive improvement. Patients with satisfactory reconstruction show stable results over time. PMID- 19476109 TI - Centralized Pan-European survey on the undertreatment of hypercholesterolaemia (CEPHEUS). AB - The CEntralized Pan-European survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS) was initiated to quantify the degree of under treatment of hypercholesterolaemia in Europe. Its primary objective was to establish the proportion of treated patients reaching the LDL-C goals according to the Third Joint European Task Force guidelines. Secondary objectives targeted subgroups of primary or secondary prevention patients and those with a metabolic syndrome. Further-more, CEPHEUS also aimed at the identification of determinants for under-treatment. Among the patients available for evaluation in Belgium (n=6276), 58.5% reached LDL-C goals as recommended by the 2003 European guidelines, 59.8% in primary prevention, 55.8% in secondary prevention, and 55.8% of those with a metabolic syndrome. The majority of patients (82.5%) was treated with statins. The univariate significant (P < 0.10) predictors of attaining LDL-C goal were the following: (a) nonsmoker, (b) no history of PAD or CAD, (c) absence of metabolic syndrome, (d) lower CV risk category, (e) absence of patient's concerns about treatment changes, (f) no withdrawal of lipid-lowering therapy when on target, (g) optimal. treatment adherence, (h) no patient's frustrations, (i) lipid-monitoring frequency, (j) physician being a specialist and (k) physicians finding it stressful to get patients on target. In an adjusted multi level model, achievement of the LDL-C goals was significantly associated with: (a) type of lipid-lowering therapy, (b) risk category the patient fell into, (c) LDL-C level before initiating treatment, (d) patient's feelings about the treatment, (e) patient's acknowledgement about current cholesterol level and (f) self-reported drug compliance. PMID- 19476110 TI - Chronic mitral regurgitation--significance of the echocardiographic determinants in predicting severity. AB - The aim of study was to determine the significance of the best echocardiographic parameters for assessing the severity of mitral regurgitation (MR). METHODS: The study population consisted of 107 patients, mean age 52 +/- 7 y with chronic isolated non-ischaemic MR. Quantification of the MR was performed using echocardiography through the proximal isovelocity surface area method (regurgitant volume (RV) and the effective regurgitant orifice (ERO) were calculated) and the assessment of vena contracta width (VCW). RESULTS: The ROC curve analysis and Peto odds used to differentiate between the significant (III IV grade) and non-significant (I-II grade) MR groups of patients indicated thatVCW, RV and ERO were the most powerful predictors of MR.The area under the ROC curve was 0.931, 0.944, 0.927, respectively.The cut-off values defining significant MR were: VCW > or =7 mm, RV > or =45 ml, ERO > or = 0.33 cm2. CONCLUSIONS: The most powerful predictors of severe MR are VCW, ERO and RV. PMID- 19476112 TI - Expression or secretion of IL-17 in the peripheral blood mononuclear cells from patients with dilated cardiomyopathy. AB - OBJECTIVE: The objective of the study was to investigate the relation between interleukin-17 (IL-17) level in the plasma and in peripheral blood mononuclear cells (PBMCs), and dilated cardiomyopathy (DCM) disease severity. METHODS AND RESULTS: 30 patients with DCM and 20 normal adults as control were studied. IL-17 protein level in plasma, PBMC culture supernatants, and phytohaemagglutinin stimulated PBMC culture supernatants were measured with ELISA. IL-17 mRNA expression in PBMCs was detected by reverse transcription-polymerase chain reaction. Results showed that the IL-17 protein level in PHA-stimulated PBMC culture supernatants or its mRNA level in the PHA-stimulated PBMC, but not in plasma or in PBMC culture supernatants, was significantly elevated in DCM patients compared with normal control subjects.The IL-17 protein level in cultured supernatants and the IL-17 mRNA level in the PBMCs were strongly correlated with the heart function of DCM patients. CONCLUSIONS: The ability to express IL-17 protein or mRNA in PBMC is abnormal and the change strongly correlates with the heart function of DCM patients. PMID- 19476111 TI - Retrospective analysis of risk factors in young patients with coronary artery disease in Guangdong and Zhejiang, China. AB - OBJECTIVES: The objective of this study is to investigate the clustering status of risk factors for young patients with coronary artery disease (CAD) and analyse the relationship between risk factors and CAD. METHODS: 168 patients with CAD aged under 45 years, 170 age-matched non-CAD individuals (angiographically normal) and 170 patients with CAD aged over 45 years were set as CAD group, control group and reference group, respectively. Plasma levels of lipids, C reactive protein (CRP), traditional risk factors (hypertension, hyperlipidaemia, diabetes, obesity, smoking) were evaluated. RESULTS: The following results were obtainted: (I) there was a significant difference in gender, proportion of smoking, TC and TG between the CAD group and the control group, and also in gender, smoking, hypertension, diabetes, BMI and blood lipids between the CAD group and the reference group (P < 0.05); (2) there was a significant difference in levels ofTG,TC, HDL-C, LDL-C and BMI (P < 0.05), but no remarkable difference in ApoB/ApoA1 and CRP between the CAD group and the reference group (P > 0.05).There were significant differences in TG, ApoB/ApoA1 and CRP (P < 0.05), but no remarkable difference in other factors between the CAD group and the control group (P > 0.05); (3) logistic regression showed a close relationship between CAD and smoking (OR = 2.5, 95% CI: 1.43-3.98), CRP (OR = 2.71,95% CI: 1.46-5.88),TG (OR = 1.58, 95% CI: 1.25-2.75) and ApoB/ApoA1 (OR = 1.93, 95% CI: 1.14-3.13). CONCLUSIONS: Smoking, CRP, ApoB/ApoA1 ratio and TG are independent risk factors for young patients with CAD. PMID- 19476113 TI - Serum levels of C-reactive protein and uric acid in patients with cardiac syndrome X. AB - OBJECTIVES: Angina-like chest pain, a positive result from a stress test, and normal coronary arteries are characteristics of patients with cardiac syndrome X (CSX). Serum levels of C-reactive protein (CRP), which is a marker of a systemic inflammatory state, are associated with coronary atherosclerosis and endothelial dysfunction. Serum uric acid (UA) levels have also been implicated in the development of atherosclerotic cardiovascular disease. However, little is known about the association of serum UA and CRP levels with CSX. METHODS: In all, 250 subjects (100 patients with CSX, 100 with coronary artery disease (CAD), and 50 control subjects) were enrolled in the study. Coronary arteries were evaluated by conventional coronary angiography in the CSX and CAD groups. All patients underwent a noninvasive stress test. To determine whether they are potential risk factors for CSX, serum CRP and UA levels were compared among the 3 groups. RESULTS: Serum levels of CRP were higher in patients with CSX or CAD than in the control subjects (4.4 +/- 3.1 and 4.5 +/- 2.9 mg/L, respectively, vs. 1.9 +/- 1.6 mg/L; P < 0.001), but those levels were similar in patients with CSX or CAD. Uric acid levels were higher in patients with CSX or CAD than in the control subjects (5.5 +/- 1.1 mg/dl and 5.9 +/- 1.4 mg/dl, respectively, vs. 4.4 +/- 1.2 mg/dl; P < 0.00 1), but those levels were also similar in patients with CSX or CAD. CONCLUSIONS: In patients with CSX, serum CRP and UA levels were as high as those in patients with CAD. Elevated serum CRP and UA levels may contribute to the development of CSX. PMID- 19476115 TI - Impact of interval versus steady state exercise on nitric oxide production in patients with left ventricular dysfunction. AB - AIM: The aim of the present study was to assess the impact of the interval exercise training (IET) vs. steady state exercise training (SSET) on nitric oxide production, through changes of circulating blood markers of endothelial function, including stable end-products of nitric oxide (NOx) and S-nitrosothiols (RSNOs) in patients with left ventricular dysfunction (LVD). PATIENTS AND METHODS: The impact of the IET vs. SSET on NOx and RSNOs production was assessed in a total of 31 (25 male, 6 female) patients with LVD (ejection fraction <40%), who were admitted to our residential rehabilitation centre. Patients were randomised into an IET group (n=18; 15 min interval exercise sessions, 2 times daily) and an SSET group (n=13; 5-10 min steady state exercise sessions, 2 times daily), and exercised every day over a period of 3 weeks. The modified Saville-Griess method was used to determine NOx and RSNOs concentrations. RESULTS: A significant increase was observed both for NOx (P < 0.05) and RSNOs (P < 0.001) in the IET group, as well as for RSNOs in the SSET group (P < 0.001). Both training methods were observed to significantly improve exercise capacity, as demonstrated for increased workload (P < 0.001 and P < 0.05 for the IET and SSET groups, respectively) and duration (P < 0.001 and P < 0.01 for the IET and SSET groups, respectively) of the exercise stress test at the end of the study. CONCLUSION: The results of the present study have demonstrated an increased nitric oxide production and improved exercise capacity in patients with left ventricular dysfunction, who were engaged in an interval exercise programme for three weeks, and clearly indicated an advantage of interval compared to steady state training method for cardiovascular rehabilitation. PMID- 19476114 TI - Non-invasive tissue Doppler imaging pulmonary capillary wedge pressure measurement improves NT-proBNP prognostic value in heart failure. AB - OBJECTIVE: The aim of the present study was to investigate whether the improvement of pulmonary capillary wedge pressure (PCWP) non-invasively assessed with tissue Doppler imaging is able to predict prognosis and cardiac-related mortality in patients with heart failure (HF), as previously demonstrated for NT proBNP. METHODS: We prospectively studied 23 patients (74 +/- 10 y; 17 M, 6 F) with acute HF. NT-proBNP and PCWP were measured at admission and discharge. NT proBNP concentrations were determined by a chemiluminescent immunoassay kit. PCWP was assessed using the ratio of transmitral E velocity to the early diastolic mitral annulus velocity (E'), with the formula PCWP = 1.9 + 1.24 (E/E'). Patients were divided in two groups according to the clinical end-point based on cardiac death and hospital readmission for HF. RESULTS: After a mean follow-up of 230 days, 10 patients reached the end-point (group A), while 13 patients resulted event-free (group B). In group B, NT-proBNP values significantly decreased (3816 +/- 7424 vs. 6799 +/- 10537 pg/mL, P < 0.01) and PCWP improved (17 +/- 7 vs. 23 +/- 12 mmHg, P < 0.01). The decrease in both NT-proBNP and PCWP values was able to identify the majority of patients (77%) with an event-free survival at follow up, whereas 70% of patients who reached the end-point had discordant changes in NT-proBNP and PCWP (chi2 = 5.06, P < 0.05). CONCLUSIONS: The combination of a biochemical marker such as NT-proBNP and a new indicator of LV filling pressure (E/E') allows to estimate the prognostic impact of standard medical therapy even in a small group of HF patients. PMID- 19476116 TI - Comparison of intracoronary adenosine and isosorbide dinitrate on no-reflow/slow flow during rotational atherectomy. AB - OBJECTIVE: To compare the effect of intracoronary adenosine and isosorbide dinitrate (ISDN) on no-reflow/slow flow during high-speed rotational atherectomy (HSRA) in patients with complex coronary artery disease (CAD). METHODS AND RESULTS: Medical records from consecutive patients diagnosed with complex CAD between November 2002 and March 2006 who underwent HSRA at the Tri-Service General Hospital, National Defence Medical Centre in Taipei, Taiwan, were included in this study. Patients in the adenosine group (n=32) received a 50 microg intracoronary adenosine bolus prior to the initiation of burr rotation and during each ablation. Patients in the ISDN group (n=58) received a 0.5 mg intracoronary ISDN bolus at comparable time points. Angiographic success was achieved in 100% of patients in the adenosine group and 98.3% (57/58) in the ISDN group.The procedural success rates were 96.9% (31/32) in the adenosine group and 89.7% (52/58) in the ISDN group. One patient (3.1%) from the adenosine group and six patients (10.3%) from the ISDN group experienced no-reflow/slow flow (P = 0.414). No in-hospital mortality occurred and target vessel revascularization was unnecessary. CONCLUSIONS: Intracoronary administration of either adenosine or ISDN during HSRA appears safe and administration of either agent may be effective in decreasing the incidence of no-reflow/slow flow during HSRA. Further large, prospective, randomized, placebo-controlled trials are required. PMID- 19476117 TI - Relationships between paced QRS duration and left cardiac structures and function. AB - BACKGROUND: In patients with congestive heart failure, QRS duration (QRSd) is correlated with left ventricular (LV) ejection fraction (LVEF), ventricular dyssynchrony and patients' prognosis. However, little is known about the relationships between paced QRS duration (pQRSd) to cardiac structures and function and ventricular dyssynchrony in patients with chronic right ventricular apical (RVA) pacing, which were investigated in this study. METHODS: Seventy patients implanted with DDD(R) pacemaker for high- or third-degree atrioventricular block were enrolled to study pQRSd and echocardiographic variables, including aortic root dimension (AO), left atrial dimension (LAD), LV end-systolic dimension (LVDs), LV end-diastolic dimension (LVDd), interventricular septum thickness (IVST), LV posterior wall thickness (LVPWT), LVEF, interventricular mechanical delay (IVMD), systolic asynchrony index (Ts-SD) and septal-to-lateral delay.The relationships between pQRSd and such variables were examined. RESULTS: The pQRSd correlated positively with LVDd (r = 0.3166, P < 0.05), LVDs (r = 0.3741, P < 0.05), LAD (r = 0.5848, P < 0.01), IVST (r = 0.2925, P < 0.05), and negatively with LVEF (r = -0.3037, P < 0.05). No significant correlations were found between pQRSd and AO, LVPWT, IVMD, Ts-SD and septal-to-lateral delay (all P > 0.05). There was no significant correlation between LVEF and IVMD, Ts-SD, septal-to-lateral delay (P > 0.05). However, IVMD, Ts-SD and septal-to-lateral delay were greater in patients with low LVEF than in patients with normal LVEF (P < 0.05). A cut-off value for pQRSd of 180 ms had a sensitivity of 85.71% and a specificity of 66.67% to detect left atrial dilation. CONCLUSION: pQRSd is correlated with left cardiac structures and LV systolic function. pQRSd > or =180 ms indicates left atrial dilation. There is no correlation between pQRSd and ventricular dyssynchrony. PMID- 19476118 TI - Ethnic differences in overweight and obesity between Han and Mongolian rural Chinese. AB - BACKGROUND: Ethnic differences in the prevalence of obesity are known to exist. However, little is known about obesity in different ethnic rural Chinese. This study was designed to investigate the epidemiologic features of overweight and obesity in Han and Mongolian rural Chinese. METHODS: A cross-sectional survey was conducted during 2004-2006, which made use of a multistage cluster sampling method to select a representative sample in Fuxin county, Liaoning province, China. 36,154 Han people and 9236 Mongolian people aged > or =35 years were examined. At baseline, lifestyle and other factors were obtained. Overweight and obesity were defined according to the World Health Organization classification and Chinese criteria, respectively. RESULTS: Using WHO criteria, 21.3% of the Han people and 26.1% of the Mongolians had overweight or obesity (P < 0.001). The corresponding figure was 33.4% of the Han people and 40.3% of the Mongolians by Chinese criteria (P < 0.001). The prevalence of overweight was significantly higher in Mongolian people than Han people (P < 0.001). Multivariate logistic regression revealed that female gender, high levels of education and current drinking status were the common risk factors for Han and Mongolian overweight or obese participants, while age > or =65 years and current smoking status were the common protective factors. Below the age of 65 years, a positive association was observed between age and overweight or obesity in Han people, but not in the Mongolian people. High levels of physical activity as a protective factor and diabetes as a risk factor were shown in Han but not in Mongolian people. CONCLUSIONS: There were ethnic differences in overweight and obesity between Han and Mongolian rural Chinese. These differences might be due to different factors between these two ethnicities such as age, physical activity and diabetes. PMID- 19476119 TI - Plasma total homocysteine concentrations in a Turkish population sample. AB - OBJECTIVES: The purpose of this study is to determine the reference of plasma total homocysteine levels from a Turkish population and to investigate the relationship of plasma total homocysteine levels with sex and age groups. DESIGN AND METHODS: Plasma total homocysteine levels were measured in 2257 Turkish individuals (1381 men and 876 women) aged 1-90 years. Plasma total homocysteine concentrations were determined using high performance liquid chromatography with fluorescence detector. RESULTS: The mean plasma total homocysteine level was significantly higher in men (mean, 10.6 micromol/L) than in women (mean, 8.7 micromol/L), P < 0.001. The mean plasma total homocysteine levels for the 1-10, 11-20, 21-30, and 31-40, 41-50, 51-60, and 61-70, 71-80, 81-90 age groups, were 6.5, 9.6, 10.1, and 10.4, 10.5, 10.9, and 11.3, 12.7, 14.6 miromol/L in men and 7.1, 7.6, 7.5, and 7.8, 8.7, 9.4, and 10.3, 11.2, 13.3 micromol/L in women, respectively. CONCLUSIONS: These data indicate the significance of sex- and age associated differences of plasma total homocysteine levels in Turkish subjects. Plasma total homocysteine levels were increasing with age and men were found to have higher levels than women, as is found in other populations. PMID- 19476121 TI - Why does the general practitioner refer patients with chest pain not-urgently to the specialist or urgently to the emergency department? Influence of the certainty of the initial diagnosis. AB - BACKGROUND: Chest pain is an initial symptom for several minor diseases but acute myocardial infarction (AMI) should not be missed. AIM: To assess the influence of initial diagnosis and degree of certainty of this initial diagnosis on the referral decision and the referral method (urgent-non-urgent) in patients contacting their GP with chest pain. STUDY DESIGN: Observational study. SETTING: The study was performed in a sentinel network of general practices in Belgium, covering almost 1.6% of the population. SUBJECTS: All patients attending their GP and complaining of chest pain during 2003. METHOD: The relationships were reported as proportions and in odds ratios (OR) with their 95% confidence intervals. RESULTS: 1996 patients were included (men 52%). Men were referred more often (OR = 1.44; 95% CI: 1.13-1.82). Age shows no relation to referral (OR = 1.06; 95% CI: 0.83-1.35) but predicts urgent referral (OR = 1.46; 95% CI: 1.02 2.08). Odds ratios in case of serious heart disease were high with 11.58 (95% CI: 5.72-23.44) when the GP was certain of his diagnosis and 2.96 (95% CI: 1.59-5.51) if not. If the GP was uncertain, in all disease categories 54% (95% CI: 48-59) of the patients were referred non-urgently. CONCLUSION: Referral rates for patients with chest pain were influenced by the initial diagnosis and the degree of certainty of this initial diagnosis. PMID- 19476120 TI - Pre-hospital statin therapy may not reduce incidence of all-cause mortality and overall MACCE during hospital stay after coronary artery bypass graft surgery. AB - BACKGROUND: The available literature has not been able to demonstrate the exact association between preoperative statin therapy and the reduction in the rates of major adverse cardiac and cerebrovascular events (MACCE). The aim of this study is to explore these unanswered questions. METHODS: A review of patients having CABG surgery between June 2003 and September 2005 (n=2013) was performed at Beijing Anzhen Hospital of the Capital University of Medical Science The preoperative demographic, morbidity and co-morbidity variability and the preoperative medications were compared between two groups: group I, on statins, n=904; group II, not on statins, n=1109. A Cox proportional hazard analysis was performed to determine the independent risk-reducing association with outcome variability after CABG surgery. RESULTS: Our study demonstrated that pre-hospital statins therapy did not reduce the risk of all-cause mortality or overall MACCE during hospital stay (1.7% versus 2.4%, respectively, P > 0.05; 4.4% versus 4.5%; P > 0.05, respectively). Compared with patients not receiving statin therapy, the hazard ratio for all-cause mortality during hospital stay was 0.696 (95% CI, 0.394-1.231, P = 0.213). The significant predictors of mortality during follow-up are age, triple-vessel CAD and blood creatinine (Cr) level. CONCLUSIONS: Pre hospital statin therapy did not reduce the risk of mortality or the rates of MACCE during in hospital stay after CABG surgery. PMID- 19476122 TI - The absence of pathological myofibre disarray in the diabetic heart: is it a paradox? AB - Myofibre disarray in progressive hypertrophic cardiomyopathy (HCM) is a well established pathological cardiac tissue change and thereby represents a biomarker for that condition. On the other hand, in diabetic cardiomyopathy, myofibre disarray historically has been reported not to occur. This is surprising given that many of the pathological, remodelling and mechanical changes that present in the diabetic ventricle are also present in HCM, for example, myocardial stiffness, myocardial hypertrophy, apoptosis, cell slippage, extensive collagen expression and fibrosis. The question therefore begs is the absence of myocyte disarray in the diabetic heart a paradox or simply an oversight? PMID- 19476123 TI - Pulmonary infundibular stenosis and ventricular septum defect: usefulness of cardiac CT. AB - A 35-year-old man with a history of syncope and echocardiographic diagnosis of right ventricular outflow tract obstruction and ventricular septum defect was submitted to complete evaluation with an Aquilion Toshiba 64-multislice CT in order to confirm diagnosis and to complete information prior to surgery. PMID- 19476124 TI - Contralateral pneumothorax after endocardial dual-chamber pacemaker implantation resulting from atrial lead perforation. AB - We describe the occurrence of a right-sided pneumothorax following a left-sided dual chamber pacemaker implantation, due to a perforation of the screw of the J shaped active-fixation lead through the right atrial wall. A review of the literature regarding complications of different atrial lead types (passive vs. active and J-shape vs. straight) is provided. Current data suggest that passive fixation leads could have an advantage, provided they can be positioned satisfactorily because of the lower risk of pericardial complications. If active fixation leads are used, straight leads might be preferable above J-shaped leads because of the lower rate of perforation. PMID- 19476126 TI - Vertebral artery stenting by using coronary intervention techniques and devices. AB - Atherosclerotic disease of the vertebro/basilar vessels is an important cause of posterior circulation infarction. Commonly, the primary atheroma forms at the origin of the vertebral arteries. Although initial treatment is medical, arch and four-vessel studies (CTA, MRA, or DSA) are warranted if symptoms continue. Endovascular management of vertebral artery stenosis might be highlighted as a good option in selected patients. This is a case of endoluminal stenting of vertebral artery with a durable result. PMID- 19476125 TI - Successful resection of a giant subpericardial lipoma with recurrent ventricular arrhythmias. AB - We report a case of a giant subpericardial lipoma with ventricular arrhythmias. It was resected through a median sternotomy without cardiopulmonary bypass. The tumour was about 21x23x5 cm and weighed 2100 g. After resection the heart rhythm returned to sinus rhythm. PMID- 19476127 TI - Bare metal or drug-eluting stent implantation in last remaining vessel PCI? A serious dilemma. AB - This case report describes the treatment of an old male diabetic patient with last remaining vessel coronary artery disease and poor left ventricular function. In presence of an old occlusion of the left main coronary artery, a subtotal stenosis of a dominant right coronary artery required angioplasty. After ample consideration it was decided to implant a bare metal stent (BMS) instead of a drug-eluting stent (DES). The major reason was the fear for early discontinuation of clopidogrel in case a drug-eluting stent was placed. The procedure and follow up are described followed by an overview of current literature concerning similar pathology. PMID- 19476128 TI - [What is new in the treatment of vitiligo]. AB - BACKGROUND: Vitiligo is a frequent hypomelanosis that affects 1% of the world population, and 0,95% of the tunisian population. OBJECTIVE: The objective of our study is to describe through a recent review of the literature, the different therapeutic modalities, now used in vitiligo. We have used a clinical approch to guid therapeutic indications. METHODS: We have performed a review of the articles, dealing with the treatment of vitiligo and published during the 10 previous years. We have used a Medline research with these key-words: "vitiligo and treatment". Randomized studies were privileged and 29 articles were analysed. We have initially presented all validated therapeutic means now used in vitiligo. We have then proposed, according to this recent review of the literature, clinical indications according to vitiligo type, extension of lesions and if vitiligo involves adults or children. RESULTS: We dispose of multiple chemical, physical and surgical treatments of vitiligo. Vitiligo with partial melanocyte defect can be treated especially by the different modalities of phototherapy (PUVAtherapy, PUVASOL, UVB therapy TL01, Laser excimer). Surgical treatments were also described, with there principal indications. Ethiopathgenic treatments (local steroids, Tacrolimus, Calcipotriol, Vitix*) were especially indicated in vitiligo with complete epidermic and follicular achromy. Finally, different therapeutic associations were reported in the litterature, showing synergic effect of some treatments. CONCLUSION: Phototherapy remains the best treatment of vitiligo type I. In vitiligo type II and III, ethiopathogenic treatments may be efficient, alone or associated with phototherapy. PMID- 19476129 TI - Spread of multidrug resistant Acinetobacter baumannii in a teaching hospital. AB - BACKGROUND: A. baumannii is an important opportunistic pathogen widely distributed in the hospital environment and responsible for a variety of nosocomial infections especially in patients from intensive care units. AIM: We describe an outbreak of Acinetobacter baumannii (16 stains) in 3 intensive care units (I, II, III) at Charles Nicolle hospital of Tunis over a 5 month period (March to July 2005). METHODS: The antimicrobial susceptibility was determined by disc diffusion test and the genetic relatedness of isolates was done by Random Amplified Polymorphic DNA (RAPD) analysis. Two strains not related to the outbreak were used for the discrimination of the technique. RESULTS: Samples were collected from blood (44%), materials (31%), pus (6.5%), urines (6.5%) and respiratory tract (12.5%). Antibiotic resistance pattern showed 2 different profiles. However, molecular typing of isolates revealed 3 distinct profiles (A, B, C) represented respectively by 8, 7 and one isolates. The major profile was the profile A found in 5 patients and in materials. It was appeared firstly in intensive care unit I, then in the 2 other units (II and III). The profile B was observed also in the 3 units. However, the profile C was found in one patient in unit I. CONCLUSION: These data emphasize the need for active surveillance for multidrug-resistant Acinetobacter baumannii, and the value of molecular typing of strains in hospital settings to investigate spread of infection. PMID- 19476130 TI - Latent autoimmune diabetes in Tunisian adults (LADA): identification of autoimmune markers. AB - BACKGROUND: LADA or type 1.5 diabetes is a slowly progressive form of autoimmune diabetes of adults. The aim of this study is to evaluate the frequency of autoimmmune markers and to identify patients with LADA among diabetics diagnosed initially as having type 2 diabetes. METHODS: Our study concerned 100 diabetics, aged between 31 and 77 years (age at onset > 30 years), with short term diabetes (duration < 6 years) and who required insulin therapy after 6 months from diagnosis of diabetes. All patients were screened for antibodies to Glutamic Acid Decarboxylase (GAD65), the Tyrosine Phosphatase (IA2) and Islet Cell antibodies (ICA). RESULTS: Mean age of patients is 53 +/- 10.5 years. Mean age at onset of diabetes was 43.3 +/- 10 years. Insulin treatment required after 3.1 +/- 1.8 years. Positivity of at least one of the auto-antibodies was found in 78% of patients. ICA were detected in 48.5% of cases. IA2 and GAD antibodies were positive respectively in 42% and 18% of tested patients. There was no significant difference of gender. Anti-GAD positive patients had statistically significant higher initial fasting blood glucose and HDL-cholesterol serum (p = 0.01 and 0.007) than those with anti-GAD negative. Patients with anti-IA2 were characterized by more important frequency of autoimmune diseases and low rate of triglycerides. The frequency of macrovascular complications was lower in ICA positive diabetics than those with ICA negative. Patients initially diagnosed as type 2 diabetes may in many cases suffer from LADA. Auto-antibodies screening may be of interest to identify LADA at the earliest stage. CONCLUSION: Frequency of type 1 diabetes in adults is underestimated. The identification of LADA may help to classify dabete and to indicate the moment of insulinotherapy. PMID- 19476132 TI - [Maintenance therapy by azathioprine after successful treatment by intravenous corticosteroid in acute severe colitis. An open prospective study]. AB - AIMS: To investigate the efficacy of azathioprine as maintenance therapy in acute severe colitis of Crohn's disease or ulcerative colitis after successful treatment by intravenous corticosteroids. METHODS: We conduct an open prospective study between 1999 and 2004. All patients with acute severe colitis and good outcome after seven at ten days of intravenous corticosteroid treatment received azathioprine (2-2.5 mg/kg/day). Rates of relapse, severe relapse and recurrence of acute severe colitis were studied and compared to patients treated between 1990 and 1998 with no azathioprine therapy after remission induced by intravenous corticosteroids. RESULTS: Between 1999 and 2004, 21 patients with acute severe colitis and favourable outcome with intravenous corticosteroid therapy received azathioprine with a mean follow-up of 26 months. Comparatively to the 22 patients with no azathioprine therapy, the rate of relapse was lower in azathioprine group (10% vs 55%; p=0.002) as well as rate of severe relapse (0% vs 36%; p=0.002) and recurrence of acute severe colitis (0% vs 27%; p =0.01). In univariate analysis, predictive factors of relapses were absence of azathioprine therapy (p=0.002 OR [IC95%]: 11.4 [2.12-61.25]), absence of decrease of levels of ESR the 3rd day of treatment (p=0.004 OR [IC95%]: 10.0 [1.79-55.63]) and absence of sigmoid involving (p=0.03 OR [IC95%]: 4.80 [1.15-19.92]). In multivariate analysis, the independent predictive factor of relapse was absence of azathioprine therapy (p=0.003 adjusted OR [IC95%]: 2.17 (1.44-6.66]). The only predictive factor of severe relapse was also absence of azathioprine therapy (p=0.002 OR [IC95%]: 2.5 [1.66-3.84]). CONCLUSION: Maintenance therapy with azathioprine is effective in prevention of relapses in patients with acute severe colitis and favourable outcome with intravenous corticosteroid therapy. PMID- 19476131 TI - [Vascular trombosis of renal graft: 9 cases]. AB - BACKGROUND: Allograft renal thrombosis can occur in 1 to 6% of cases. Many predisposing factors has been identified especially alteration of coagulation. AIM: We analyzed in this study frequency and predisposing factors of renal graft thrombosis. METHODS: We report a retrospective study including 319 renal transplant recipients. RESULTS: Nine patients (2.8%) presented veinous graft thrombosis in 5 cases and arterial thombosis in 4 cases. There were 6 men and 3 women aged of 30.6 years meanly (10-56) which developed the thrombosis 6 days (1 48) after the transplantation. All patients were detransplanted after 16.2 days and 1 patient died. CONCLUSION: Thrombosis constitute an important cause of graft loss. A perfect surgical technic and prophylactic treatment in high risk patients are necessary to reduce this complication. PMID- 19476133 TI - [Prenatal ultrasound aspects of arthrogryposis multiplex congenita]. AB - AIM: To analyze the contribution of prenatal ultrasound in the diagnosis of arthrogryposis multiplex congenital according to its type and antenatal expression. METHODS: Retrospective study led between January 1993 and November 2007. We studied the cases of arthrogryposis suspected or diagnosed by antenatal ultrasound while analyzing the circumstances of discovery, the profile of the pregnant women and the abnormal scan findings. RESULTS: 16 observations have been collected. We recovered one multiple pterigium syndrome and five observations of severe fetal akinesia sequences diagnosed in the second trimester. The arthrogryposis was part of different syndromes in other cases. Four distal arthrogryposis had been diagnosed in the second trimester. All cases suspected during the third trimester were associated to an anomaly of the amniotic fluid, mainly to a polyhydramnios. The abnormal scan findings were less specific to this term. CONCLUSION: Arthrogryposis multiplex congenital is rare. It has several morphological aspects. Some ultrasound aspects are specific in the first and second trimesters. The diagnosis is more difficult at the third trimester. PMID- 19476134 TI - [Are there any predictive factors for successful intracytoplasmic sperm injection. Statical analysis of 339 cycles]. AB - BACKGROUND: Intracytoplasmic sperm injection (ICSI) outcome is tightly depinding of male and female factors. The assesment of several clinical and laboratory parameters may predict results of ICSI. AIM: This study aimed at investigation wich parameter(s) may predict successful intracytoplamic sperm injection for infertility. METHODS: We restrospectively analysed patients who had intracytoplasmic sperm injection for male or female factor infertility. The clinical and laboratory factors that influenced the fertilization, pregnancy and implantation rates were also analysed. Three hundred and thirty nine cycles in 269 couples were analysed. Women's age, etiology of infertility, duration of infertility, number of retrived oocyts, sperm parametres and number of transferred embryos were evaluated. RESULTS: Optimal pregnancy rates were observed in women aged 25-35 years, with gradual decline with advanced age (p=0.049). The pregnancy/transfer rate was statistically depending of, the numbre of retrieved oocytes (p<0.001) and the numbre of transferred embryos (p<0.001). However, transferring more than three embryos was no significatively superior to two or three. Etiology of infertility had no influence in fertilization and pregnancy, but may predict the implantation rate (p=0.042). The duration of infertility was of no value in predecting the fertilization, implantation or pregnancy rates, and neither seam's to be the sperm parameters. CONCLUSION: The only statitically significant variables of ICSI outcome were women partner's age, numbre of retrived oocytes and numbre of transferred embryos. PMID- 19476135 TI - Virological response of Tunisians patients treated by peginterferon plus ribavirin for chronic hepatitis C: a preliminary study. AB - BACKGROUND: Peginterferon plus ribavirin is actually the most effective therapy for chronic hepatitis C. AIM: This study was designed to evaluate the efficacy and safety of peginterferon and ribavirin combination therapy in Tunisian patients with chronic hepatitis C and to identify predictors of response to treatment. METHODS: Fifty patients with chronic HCV infection recruited from the gastroenterology department of Habib Thameur hospital between January 2003 and March 2006 were prospectively included. All patients received peginterferon alpha 2a or alpha 2b subcutaneously respectively at a dose of 180 microg or 1.5 microg/Kg once weekly plus oral ribavirin given in two divided doses per day at a dose of 1000 mg/day for patients weighing 75 Kg or less and 1200 mg/day for those weighing more than 75 Kg. The clinical endpoints were the end of treatment response (EOT) and the sustained virological response (SVR) defined as an undetected serum HCV RNA 6 months after the end of treatment (< 600 IU/ml). Items associated with the main dependant variable (virological response (EOT and SVR) such us sex, age, body mass index, pretreatment viral load, pretreatment ALT quotient, pretreatment histologic degree of fibrosis, activity, steatosis, and HCV genotype (1 vs. non-1) were studied in an unvaried analysis. RESULTS: A total of 50 patients were included in the study. The mean age of patients was 47.64 +/- 8.54 years. Thirty three patients were infected by HCV genotype 1 (66%) and 15 patients by HCV genotype 2 (30%). Forty five patients (90%) had normal ALT values at the end of treatment. At the end-of-treatment 82% of patient had virologic responses. Seventy three percent of patients with HCV genotype 1 had an end-of treatment (EOT) virologic response and 52% had sustained virologic response (SVR). In patients with HCV genotypes 2 or 3, EOT and SVR were obtained respectively in 100%and 81% of patients. Only one patient infected by HCV genotype 4 was included in this study, she achieved an EOT virologic response whereas the SVR wasn't assessed. Among the 41 patients with EOT virologic response, 3 patients (7.31%) relapses during the 6 months after the end of therapy. Nine patients didn't achieve virologic response. Treatment was well tolerated for 80% of patients. Laboratory abnormalities were observed in 12 of the 50 included patients (24%) and 7 patients experienced severe adverse events during the treatment period. CONCLUSION: Combination therapy with peginterferon plus ribavirin for HCV infection was effective and safe. Careful monitoring of treatment-associated adverse events is necessary to avoid withdrew of therapy and to maintains a reasonable quality of life. PMID- 19476136 TI - Endoscopic ultrasonography versus helical CT in diagnosis and staging of pancreatic cancer. AB - AIM: Compare the performances of EUS to helical CT in the diagnosis and staging of pancreatic adenocarcinoma. METHODS: Forty two consecutive patients (mean age 63 years; 25 men, 17 women) who had surgical exploration and histologically proved pancreatic cancer were retrospectively included. All our patients underwent with endoscopic ultrasonography (EUS) and helical computed tomography (helical CT). Data analysis compared helical CT, EUS with the surgical data with or without histological study in diagnosis, staging and resectability of pancreatic cancer. Surgical findings were used as gold standard. RESULTS: For positive diagnosis EUS was more sensitive 100% (CI:93-100) than helical CT 88% (CI:77-95). But helical CT was more specific 89% (CI:64-98) than EUS 83% (CI:58 96) for small tumors whose diameter is below 2.5 cm in witch EUS was more sensitive in their detection (100% versus 83%). In evaluating venous involvement EUS was more sensitive than helical CT (96% versus 50%; p<0.05), while CT was more specific (81% versus 75%; p<0.05). Regarding lymph nodes invasion, the two imaging technique had the same sensibility (56%) with better specificity for helical CT (83% versus 75%; p<0.05). The accuracy of EUS in identifying the T and N stages were 80% and 67% respectively, while helical CT have an accuracy of 50% and 71% respectively. EUS and helical CT correctly identified all resectable tumors while EUS was more accurate than helical CT in detecting non resectable tumors 94% versus 69%. CONCLUSION: EUS remains superior to helical CT in positive diagnosis of pancreatic adenocarcinoma especially for small tumors and also for the diagnosis of venous invasion and in identifying non resectable tumors. The two techniques have the same accuracy in the detection of lymph node involvement. PMID- 19476137 TI - [Morbidity of the elderly in inpatient rheumatology clinic]. AB - BACKGROUND: The improvement of life expectation in our country explains at least in part the increase of the proportion of the elderly in hospitalized patients. AIM: The aim of this study was to identify the main diseases leading to hospitalization of the aged in a rheumatology department, to establish their clinical profiles and to evaluate the quality of their management. METHODS: Retrospective chart review about the elderly (age > or =65 years) admitted in the rheumatology department of the Charles Nicolle Hospital during a 2-year-period [January 2003-December 2004]. RESULTS: Among the 831 patients admitted to our inpatient clinic during that period, 86 were 65-year-old or more representing 10% of the total. Mean age was 71.2 years [65-88]. The sex ratio was 1/3. A history of a mean of two associated diseases [0-5] was noted. They were dominated by hypertension (50%) and diabetes (26.7%). Almost 1/3 of the elders had a surgical history. Gastro-intestinal troubles have been noted in only 19% of cases. The main cause of hospitalization was a diagnosis exploration (77.6%). The remainings were admitted for therapeutic adjustment. The disease was evolving since in mean 16 months (15 days-15 years). The mean duration of hospitalization was 21.2 days (4-60). The pathologies involved were varied dominated by degenerative rheumatisms (26.7%) with a predilection to lumbar spine, systemic diseases: 18 cases (20.9%) with 13 cases of rheumatoid arthritis, and malignant bone diseases (18.7%). At least two rheumatic diseases were found together in 49 patients (57%). The clinical findings were atypical in almost half cases (42.4%) in such aged patients. Besides drugs prescribed for non rheumatic diseases, our patients took a mean of 3.4 drugs (1-8) as symptomatic, adjuvant or etiologic treatment. The treatment observance was good in 74.4% of cases. Iatrogenic incidents occurred in 14 cases (16.2%). The outcome was favorable in 68.9% of cases. Twelve of our patients necessitated a third help. Half of our patients (54%) were controlled in our outpatient clinic 1-2 months after their issue, 12 have been hospitalized for the same disease, 8 deceased, and 19 have been lost. CONCLUSIONS: The management of the elderly patients in hospitalization must be multidisciplinary. It should take into account the clinical and therapeutic particularities of such a population. Prevention remains the best guarantee for a good quality of life and to decrease social and economic costs. PMID- 19476138 TI - [Vascular profile of patients with normal tension glaucoma]. AB - BACKGROUND: Glaucoma can be caused by multiple factors essentially the vascular factors. AIM: The aim of this article is to study the vascular profil of patients with normal tension glaucoma in the purpose to better understanding his pathogenesis and to making appropriate therapeutic decision. METHODS: 39 patients with normal tension glaucoma were investigated. Each patient had complete ophtalmologic examination with visuel field examination, a medical examination, a biological investigation and a vascular supraaortic doppler. RESULTS: One or several vascular risk factor are found in the majority of our patients. 25% of the patients aggravate their visuel fiel. 40% are diabetic, 56% are hypertensive, 40% have a lipidic disturbance and 30% have a vasospastic syndrom. CONCLUSION: Vascular risk factors play an important role in the physiopathology of normal tension glaucoma, and the prognosis depend on the treatment of these factors. PMID- 19476139 TI - [Recurrent upper respiratory tract infections in children and allergy. A cross sectional study of 100 cases]. AB - BACKGROUND: Upper respiratory tract (URT) infections are common in children. The knowledge of their risk factors allows in some cases better management. The aim of our study is to evaluate the role of allergy in this pathology. METHODS: Through a cross-sectional study about 100 children having recurrent URT infections, we evaluated the prevalence of allergy in order to find a relation between the two pathologies in general, and between allergy and each recurrent pathology. The results were compared with those of a reference group involving 164 children. RESULTS: Our study confirms a statistically significant association between allergy and recurrent URT infections (p=0.01), also between allergy and rhinopharyngitis (p=0.02), rhinosinusitis (p=0.001) and acute otitis media (p=0.01). CONCLUSION: Allergy represents a risk factor for recurrent URT infections, particularly for rhinopharyngitis, rhinosinusitis and acute otitis media. Adequate management of allergy may consequently be beneficial for the treatment and the prevention of these infections. PMID- 19476140 TI - [Clinical and therapeutic results of a retrospective study about 62 cases of epithelial ovarian carcinomas]. AB - AIM: To report retrospectively the therapeutic results and prognostic factors of epithelial ovarian carcinomas throughout a serie of 62 patients treated between 1993 and 2002. METHODS: Patients were treated with primary surgery classified as optimal (complete), sub-optimal or minimal. Adjuvant ciplatin based poly chemotherapy (6 cycles) was indicated in FIGO stage Ic or more. Patients with minimal surgery received 3 or 4 cycles of chemotherapy followed by an interval debulking surgery. Overall survival was calculated according to Kaplan-Meier and univariate analysis done by the Log-Rank test for the following factors: age group, surgical excision, stage, histological type and presence or not of ascitis at diagnosis. RESULTS: Fifty five patients were operated. The excision was optimal, suboptimal and minimal in respectively 19.3%, 33.8% and 40.3% of the cases. Adjuvant or neoadjuvant chemotherapy was given to 50 patients (93.5%). Interval debulking surgery was complete in 7 among 13 patients. At the first evaluation, 14/58 patients were in complete response. The 3 and 5 years overall survival rates were respectively of 25% and 13%. Advanced stage was the only pejorative prognostic factor (P= 0.0002). CONCLUSION: Incomplete surgery (minimal) and chemotherapy without taxanes based chemotherapy were associated with poor outcome in our patients. Our study confirmed the importance of disease stage as a prognostic factor. PMID- 19476141 TI - [Neonatal prognosis of second twin]. AB - BACKGROUND: Twin pregnancy is associated to high neonatal morbidity particularly for the second twin. AIM: To assess twin delivery practice in our department and prognosis of second twin. METHODS: Retrospective study of medical files of parturition women with twin pregnancy between January 2003 and December 2006. Were excluded women delivered before 28 weeks gestation, twin pregnancies with death or malformation of one of twins. Descriptive and comparative analyses were realised. RESULTS: One hundred forty six twin pregnancies were counted. Vaginal delivery was attempted with 90 parturition women with 85.5% of success. Caesarean section delivery rate was 47.2%. Overall there's no difference between twins considering neonatal complication. In case of vaginal delivery, the second twin's 5 minutes Apgar score was statistically under the one of the 1st twin if compared to the caesarean section delivery. This difference was no more significant if regarding the Apgar score under 7 at 5 minutes. Apgar score of the second twin was also under the one of the first twin in non cephalic presentation. CONCLUSION: Vaginal delivery of twin pregnancy was noot associated to high risk for twins. Obstetrical manoeuvres should be well controlled to reduce obstetrical trauma. PMID- 19476142 TI - Congenital lobar emphysema. Report of 17 cases. AB - The aim of this report is to determine frequency and clinical characteristics of Congenital lobar emphysema (CLE) at Children's Hospital of Tunis. METHODS: Cases of CLE managed between January the 1st 1994 until December the 31st 2004 were reviewed. RESULTS: Amongst 31 cases of cystic pulmonary malformations we report 17 CLE. They were 12 males and 5 females. The mean age at diagnosis was 41/2 months (20 days, 22 months). Symptoms were: progressive respiratory distress (n=11) recurrent attacks of dyspnea (n=5); pulmonary infection (n=1). Chest X ray and CT scans showed hyper aeration of the affected lobes. Three patients had two affected lobes. CLE was associated to bronchogenic cyst (n=2) and to congenital cardiac anomalies (n=3). All patients underwent lobectomy. Post operative course was uneventful in 16 children. CONCLUSION: CLE is an uncommon cause of respiratory distress in neonates and infants. CLE is the most common cystic pulmonary malformation in our institution. PMID- 19476143 TI - [Imaging in clinical practice]. PMID- 19476144 TI - A case of spinal immature teratoma. AB - We report a rare case of intradural immature teratoma in 2-year-old girl, interesting conus medullaris to sacrum, worsening neurological deficits. The neoplasm discovered by magnetic resonance imaging, was completely resected. We describe the clinical, radiological and pathological findings of this tumor with a review of the Literature and we insist in the difficulty of treatment. PMID- 19476145 TI - [Primary carcinoid hepatic tumour: a case report]. AB - BACKGROUND: Primary carcinoid tumour of the liver is rare and poses a diagnostic and management dilemma. AIM: Report a new cases. CASE REPORT: A 48 year-old patient man, with an 8-months history of abdominal pain and weight loss, was operated on in December 2000, in another centre with the diagnosis of caudate pancreatic cancer. At laparotomy, Resection was deemed to be not feasible. Histological examination of biopsy was for carcinoid tumor. The patient underwent post operative radiotherapy and four courses of chemotherapy and he was referred to our hospital. Physical examination was normal. Based on radiological examination, the diagnosis was endocrine tumor of the pancreas. The patient underwent relaparotomy, the lesion was independent from the pancreas but linked to the liver; the caudate lobe. Complete macroscopic resection was performed. Histological examination of operative specimen concludes to carcinoid tumor with invasion of hepatic margins. The patient underwent adjuvant chemotherapy; he was free from disease 6 months after surgery. CONCLUSION: The diagnostic of primary carcinoid tumors is based principally in the histopathological confirmation of neuroendocrine origin and the exclusion of non hepatic primary tumour. This requires preoperative imaging but most importantly a thorough laparotomy and rigorous follow-up. Surgical resection if possible is recommended. PMID- 19476146 TI - [Erdheim-Chester disease multivisceral form with favourable outcome]. PMID- 19476148 TI - [Pancreatic hydatid cyst. Diagnostic and therapeutic management]. PMID- 19476147 TI - [Cerebral ganglioglioma: a case report]. PMID- 19476149 TI - [Horizontal fracture of the talus. A case report]. PMID- 19476150 TI - [Infectious endocarditis on probe of pace maker]. PMID- 19476151 TI - [Control of several maxillomandibular brown tumours after parathyroidectomy]. PMID- 19476152 TI - [Intestinal and lymphanode involvement of Whipple's disease. One case report]. PMID- 19476153 TI - [Synchronous tumor of the stomach: association of mucosa-associated lymphoid tissue lymphoma and adenocarcinoma. About two cases]. PMID- 19476154 TI - [Localized amyloidosis of the upper aerodigestive tract about three cases]. PMID- 19476155 TI - [Choriocarcinoma revealed by pulmonary and bone metastasis]. PMID- 19476156 TI - [Primary pulmonary marginal zone B-cell lymphoma of malt type]. PMID- 19476157 TI - [Pulmonary haemosiderosis and celiac disease]. PMID- 19476158 TI - [Acute pericardite which has occurred during the treatment of chronic hepatitis C by the interferon alpha2A]. PMID- 19476159 TI - [Systemic lupus erythematosus associated to erythema multiforme like lesions: Rowell's syndrome?]. PMID- 19476160 TI - [Subungual squamous cell carcinoma of the thumb]. PMID- 19476161 TI - [Sebaceous carcinoma of the supracilium]. PMID- 19476162 TI - Bilateral tubal ectopic pregnancy and failed methotrexate therapy: a case report. PMID- 19476163 TI - Long-duration head-down bed rest: project overview, vital signs, and fluid balance. AB - INTRODUCTION: Spaceflight has profound effects on the human body. Many of these effects can be induced with head-down bed rest, which has been a useful ground based analog. With limited resources aboard the International Space Station for human research, the bed rest analog will be a primary platform on which countermeasures will be developed and tested for lunar and Mars mission scenarios. METHODS: NASA Johnson Space Center, in conjunction with the University of Texas Medical Branch (UTMB), has created the NASA Flight Analogs Project (FAP), a research program with the overall objective of using head-down bed rest to evaluate, compare, and refine candidate countermeasures to spaceflight deconditioning. This paper serves as an overview and describes the standard conditions, the standard set of subject screening criteria, and the standard set of measurements for all FAP bed rest subjects. RESULTS: Heart rate and diastolic pressures decreased transiently at the onset of bed rest. Fluid balance showed an early diuresis, which stabilized within 3 d. In this supplement, detailed results from multiple disciplines are presented in a series of reports. DISCUSSION: The following reports describe multi-disciplinary results from the standard measurements by which the responses to bed rest will be assessed and by which countermeasures will be evaluated. The data presented in this overview are meant to serve as a context in which to view the data presented in the discipline specific manuscripts. The dietary support and behavioral health papers provide additional information regarding those aspects of implementing bed rest studies successfully. PMID- 19476164 TI - Dietary support of long-duration head-down bed rest. AB - INTRODUCTION: Dietary control and nutrient intake are critical aspects of any metabolic study, but this is especially true in the case of bed rest studies. We sought to define nutritional requirements, develop menus, and implement them during long-duration head-down bed rest studies. METHODS: The dietary goals were to provide 100% of subjects' nutrient requirements and to maintain subjects' bodyweight to within 3% of their weight on the third day of head-down bed rest. The research dietitian and metabolic kitchen staff are an important part of the multidisciplinary team required to implement a bed rest study. RESULTS: We report herein the planning steps and nutrient intake results from 13 subjects. We also provide insight into some of the dietary challenges that arise during long duration bed rest studies. DISCUSSION: Regardless of the overall objective of the bed rest study to be performed, nutrition must be carefully planned, implemented, and monitored to prevent results from being compromised. PMID- 19476165 TI - Nutritional status assessment before, during, and after long-duration head-down bed rest. AB - INTRODUCTION: Bed rest is a valuable ground-based model for many of the physiological changes that are associated with spaceflight. Nutritional changes during and after 60 or 90 d of head-down bed rest were evaluated. METHODS: A total of 13 subjects (8 men, 5 women; ages 26-54 yr) participated in either 60 or 90 d of bed rest. Blood and urine were collected twice before bed rest and about once per month during bed rest. Samples were stored frozen and batch analyzed. Data were analyzed using repeated-measures analysis of variance. RESULTS: During bed rest, markers of bone resorption (such as N-telopeptide excretion, P < 0.001) increased and serum concentration of parathyroid hormone decreased (P < 0.001). Also, oxidative damage markers such as superoxide dismutase increased (P < 0.05), and after 90 d of bed rest, total antioxidant capacity decreased (P < 0.05). During bed rest, iron status indices showed patterns of increased iron stores with a decreased concentration of transferrin receptors (P < 0.01). DISCUSSION: These changes are similar to some of those observed during spaceflight, and further document the utility of bed rest as a model of spaceflight. PMID- 19476167 TI - Cardiovascular adaptations to long-duration head-down bed rest. AB - INTRODUCTION: Orthostatic hypotension is a serious risk for crewmembers returning from spaceflight. Numerous cardiovascular mechanisms have been proposed to account for this problem, including vascular and cardiac dysfunction, which we studied during bed rest. METHODS: Thirteen subjects were studied before and during bed rest. Statistical analysis was limited to the first 49-60 d of bed rest and compared to pre-bed rest data. Ultrasound data were collected on vascular and cardiac structure and function. Tilt testing was conducted for 30 min or until presyncopal symptoms intervened. RESULTS: Plasma volume was significantly reduced (15%) by day 7 of bed rest. Flow-mediated dilation in the leg was significantly increased at bed rest day 49 (6% from pre-bed rest). Arterial responses to nitroglycerin differed in the arm and leg, but did not change as a result of bed rest. Anterior tibial artery intimal-medial thickness markedly decreased at bed rest days 21 (21%), 35 (22%), and 49 (19%). Several cardiac functional parameters, including isovolumic relaxation time (73 ms to 85 ms at day 7) and myocardial performance index, were significantly increased (0.41 to 0.49 by day 7 of bed rest; indicating a decrease in cardiac function) during bed rest. There was a trend for decreased orthostatic tolerance following 60 d of bed rest (P = 0.1). DISCUSSION: Our data suggest that bed rest altered cardiovascular structure and function in a pattern similar to short-duration spaceflight. Additionally, the vascular alterations were primarily seen in the lower body, while vessels of the upper body were unaffected. PMID- 19476166 TI - Skeletal effects of long-duration head-down bed rest. AB - INTRODUCTION: Skeletal unloading during spaceflight causes regional loss of bone mineral density (BMD), primarily in the spine and lower body regions. This loss of skeletal mass could adversely affect crew health during and after spaceflight and jeopardize mission success. Bed rest has long been used as a spaceflight analog to study the effects of disuse on many body systems, including the skeleton. This study was undertaken by the NASA Flight Analogs Project (FAP) to collect control data for upcoming countermeasure studies. METHODS: There were 13 subjects who participated in 42, 44, 49, 52, 60, or 90 d of continuous, head-down bed rest. DXA scans (dual-energy X-ray absorptiometry) were obtained before and after bed rest to measure changes in BMD of the whole body, lumbar spine, hip, heel, and wrist; the 90-d subjects were also scanned at the 60-d time point. Follow-up DXA scans were performed after 6 mo and 12 mo of reambulation to assess BMD recovery. RESULTS: BMD changes were consistent with earlier bed rest and spaceflight studies, with statistically significant losses averaging 1% per month in the hip, pelvis, and heel. Recovery data were also consistent with data obtained after spaceflight. Bone biomarker data are described, and support the findings of previous studies. Specifically, the process of normal bone remodeling is uncoupled: increased bone resorption with no concomitant change in bone formation. CONCLUSION: The FAP appears to be a valid test bed for skeletal disuse studies, and should provide a useful research platform for evaluating countermeasures to spaceflight-induced bone loss. PMID- 19476168 TI - Immune status, latent viral reactivation, and stress during long-duration head down bed rest. AB - INTRODUCTION: As logistical access for space research becomes more limited and NASA prepares for exploration-class missions, ground-based spaceflight analogs will increase in importance for biomedical countermeasures development. A monitoring of immune parameters was performed during the NASA Flight Analogs Project bed rest study (without countermeasure); to establish 'control' data against which future studies (with countermeasure) will be evaluated. Some of the countermeasures planned to be evaluated in future studies may impact immune function. METHODS: The immune assessment consisted of: leukocyte subset distribution, early T cell activation, intracellular cytokine profiles, latent viral reactivation, virus specific T cell levels and function, stress hormone levels, and a behavioral assessment using stress questionnaires. RESULTS: In general, subjects did not display altered peripheral leukocyte subsets, constitutive immune activation, altered T cell function, or significant latent viral reactivation (EBV, VZV). Levels of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) decreased during the study. Cortisol levels (plasma and saliva) did not vary significantly during 90-d bed rest. CONCLUSIONS: These data demonstrate the absence of significant immune system alteration and physiological stress during 90-d bed rest, and establish control data against which future studies (including countermeasures) may be compared. PMID- 19476169 TI - Postural reflexes, balance control, and functional mobility with long-duration head-down bed rest. AB - INTRODUCTION: Spaceflight has functionally significant effects on sensorimotor behavior, but it is difficult to separate the effects of ascending somatosensory changes caused by postural muscle and plantar surface unloading from descending visual-vestibular neural changes. To differentiate somatosensory changes from graviceptor changes in post-spaceflight sensorimotor behavior, bed rest may serve as an exclusionary analog to spaceflight. METHODS: Four separate tests were used to measure changes in sensorimotor performance: 1) the monosynaptic stretch reflex (MSR); 2) the functional stretch reflex (FSR); 3) balance control parameters associated with computerized dynamic posturography (CDP); and 4) a functional mobility test (FMT). RESULTS: A mixed model regression analysis showed significant increases in median MSR start and peak latencies, while the median FSR latency showed no significant increase. Median MSR peak magnitude showed a significant increase during the middle bed rest period (19-60 d). There were no significant effects of bed rest on balance control, but some indication that dynamic head movements may affect posture after bed rest. Time to complete the course for the FMT increased significantly with bed rest. DISCUSSION: The four primary tests indicate that long-duration head-down bed rest, through unloading and modification of the body's support surface, serves as an exclusionary analog for sensorimotor responses to spaceflight. Furthermore, the data suggest that procedures designed to alleviate modifications to the sensory substrate serving the soles of the feet may provide a countermeasure to help maintain support afferentation of the postural muscles. PMID- 19476170 TI - Behavioral and psychological issues in long-duration head-down bed rest. AB - INTRODUCTION: This report is one of a series on the Flight Analogs Project, which is designed to lay the groundwork for a standard bed rest protocol. Behavioral health services, similar to those offered to the U.S. astronauts who undertake 6 mo missions onboard the International Space Station, were provided to 13 long duration head-down bed rest participants. Long-duration missions pose unique challenges and stressors, including separation from primary support group, monotonous environment, and loss of privacy and autonomy. METHODS: The psychological services team, consisting of a psychiatrist, a psychologist, and a master's level psychological support scientist, provided behavioral health services throughout all phases of the Flight Analogs Project (FAP) long-duration head-down bed rest study. During the initial screening phase, potential candidates completed 4 h of psychological testing and a 1.5-h clinical interview with a psychologist to assess their psychological fitness and ability to complete the study successfully. Additionally, the psychological services team provided pre-admission trainings on time management, stress management, and communication skills and conflict resolution. Throughout their stay on the research unit, study participants received regular individual and group visits from the psychological services team. Training was also provided to study personnel to address personality and behavioral management challenges. RESULTS: Psychological support and training provided to both subjects and study personnel have successfully improved the well being of study participants. DISCUSSION: Behavioral health services are indispensable to long-duration head-down bed rest studies. PMID- 19476171 TI - Cognitive functioning in long-duration head-down bed rest. AB - INTRODUCTION: This report is one of a series on the Flight Analog Project, which is designed to lay the groundwork for a standard bed rest protocol. The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is a self administered battery of tests used on the International Space Station for evaluating cognitive functioning. Here, WinSCAT was used to assess cognitive functioning during extended head-down bed rest. METHODS: There were 13 subjects who participated in 60 or 90 d of head-down bed rest and took WinSCAT during the pre-bed rest phase, the in-bed rest phase, and the post-bed rest (reconditioning) phase of study participation. RESULTS: After adjusting for individual baseline performance, 12 off-nominal scores were observed out of 351 total observations during bed rest and 7 of 180 during reconditioning. No evidence was found for systematic changes in off-nominal incidence as time in bed rest progressed, or during the reconditioning period. DISCUSSION: Cognitive functioning does not appear to be adversely affected by long-duration head-down bed rest. Individual differences in underlying cognitive ability and motivation level are likely explanations for the current findings. PMID- 19476172 TI - The humeral head as a potential donor source for osteochondral allograft transfer to the knee. AB - This study aimed to determine whether osteochondral allograft plugs from the humeral head are a good topographic match to recipient sites on the femoral condyle. If so, the donor pool for allograft osteochondral transplantation to the knee may increase. Simulated osteochondral grafts of 1-cm, 1.5-cm, and 2-cm diameters were taken from the surface map of the humeral heads and superimposed and optimized on recipient sites of identical size on the femoral condyles. Primary measurement criteria included contour mismatch and circumferential step off. These measurements increased with donor plug size. For the 1-cm and 1.5-cm plugs, the lowest mean mismatch (0.068 mm and 0.110 mm, respectively) and step off (0.057 mm and 0.154 mm, respectively) occurred at the 30 degree medial position. For the 2-cm plugs, the lowest mean mismatch (0.183 mm) and step-off (0.227 mm) occurred at the 60 degree lateral position. Although 1-cm osteochondral plugs were a good topographic match to the recipient sites, the 2 cm plugs had a mismatch approaching 0.5 mm, an offset with a demonstrated peak contact pressure > 40% higher than normal. The topographic match of the humeral head suggests it is a potential donor source for osteochondral allograft transfer to the distal femur. PMID- 19476173 TI - The graft/femoral tunnel angles in posterior cruciate ligament reconstruction: a comparison of 3 techniques for femoral tunnel placement. AB - This study compared the graft/femoral tunnel angle produced with the outside-in technique with the inside-out technique at 90 degrees and 120 degrees of flexion. Three femoral tunnels were marked with guidewires and measured radiographically in 8 fresh-frozen cadaveric knees using both techniques. Results were analyzed. The mean graft/femoral tunnel angle was 34.4 degrees +/- 14.4 degrees for the outside-in technique, 52.3 degrees +/- 14.1 degrees for the inside-out technique at 120 degrees of flexion, and 74.4 degrees +/- 11 degrees for the inside-out technique at 90 degrees of flexion. The angle was smaller for the outside-in technique versus the inside-out technique at both 120 degrees (P = .019) and 90 degrees of knee flexion (P < .001). The outside-in technique for femoral tunnel placement produces the lowest graft/femoral tunnel angle in cadavers. With the inside-out technique, 120 degrees of flexion produces smaller angles than does 90 degrees of flexion. The outside-in technique results in lower angles and perhaps lower graft failure rates. However, additional clinical studies are needed. PMID- 19476174 TI - A biomechanical analysis of bone-patellar tendon-bone grafts after repeat freeze thaw cycles in a cyclic loading model. AB - The purpose of this study was to examine the biomechanical effects of bone patellar tendon-bone (BPTB) grafts subject to repeat freeze-thaw cycles in a cyclic loading model. We hypothesized that repeat freeze-thaw cycles have deleterious effects on the tensile properties of BPTB grafts. Thirty BPTB composite grafts were harvested from porcine knee specimens. Tendons were randomized into 3 groups: fresh, 1 freeze-thaw cycle (-80 degrees C), or 2 freeze thaw cycles. The grafts were cyclically loaded to simulate the forces on the anterior cruciate ligament during walking and running, prior to single cycle load to-failure testing. All tendon failures were mid-substance and occurred during the single cycle load-to-failure testing. There was no statistically significant difference in ultimate stress or strain between the groups. Repeat freeze-thaw cycles do not have deleterious effects on the tensile properties of BPTB grafts in a cyclic loading model. Potential influence on biologic graft healing or integration remains unknown. PMID- 19476175 TI - Autologous bone effects on femoral tunnel widening in hamstring anterior cruciate ligament reconstruction. AB - This study examines the hypothesis that autologous bone in the femoral tunnel for a hamstring anterior cruciate ligament (ACL) reconstruction will reduce femoral tunnel widening. Thirty-six patients undergoing hamstring autograft ACL reconstruction were randomized to 2 groups. One group underwent ACL reconstruction using EndoButton femoral fixation. The other group underwent the same procedure, with the addition of a bone plug placed at the aperture of the femoral tunnel next to the graft. Twenty-seven patients at > 6 months postoperatively (range, 6-12 months) had digitized anteroposterior (AP) and lateral radiographs of the involved knee. Tunnel widening was determined by comparing the radiographic tunnel diameters to the drilled tunnel diameters from surgery. The mean (+/- SD) tunnel enlargement on the AP radiographs in the standard and plug groups were 3.8 +/- 1.7 mm and 3.5 +/- 2.0 mm, respectively (P = .61). On lateral radiographic assessment, the mean (+/- SD) tunnel enlargement in the standard and plug groups were 3.3 +/- 1.9 mm and 3.4 +/- 2.2 mm, respectively (P = .90). Autologous bone plug graft during ACL reconstruction does not reduce femoral tunnel widening. PMID- 19476176 TI - Intra-tunnel fixation versus extra-tunnel fixation of hamstring anterior cruciate ligament reconstruction: a meta-analysis. AB - Hamstring anterior cruciate ligament (ACL) reconstructions fixed inside both bone tunnels have a shorter initial working length, and thus should be stiffer than those fixed outside both bone tunnels. We used meta-analysis to compare 4 stranded hamstring ACL reconstructions using the 2 fixation methods with reconstructions using patellar tendon autografts. A Medline database search of English-language articles published through June 2004 yielded 36 studies that met the inclusion criteria: 5 intratunnel fixation studies (569 patients), 10 extra tunnel fixation studies (604 patients), and 24 patellar tendon studies (1592 patients). Three studies included both patellar tendon and hamstring reconstructions. Demographically, all 3 groups were similar. There was no significant difference in the percentage of knees restored to normal instrumented laxity measurements between the 3 groups, nor was there a difference in graft failure rate. Patient satisfaction and return to preinjury activity rates were similar between the intratunnel fixation and patellar tendon groups and were significantly lower for the extra-tunnel fixation group. Good International Knee Documentation Committee scores did not correlate with good patient satisfaction or return to preinjury activity. PMID- 19476177 TI - Reduced blood loss after total knee arthroplasty with local injection of bupivacaine and epinephrine. AB - Our goal was to determine by direct measurement of drain output whether intraoperative injection of bupivacaine with epinephrine significantly reduces postoperative blood loss in total knee arthroplasty (TKA). The study and control groups were primary TKAs performed by 1 surgeon using a single-cemented TKA design and a consistent postoperative protocol. The study group comprised 37 sequential TKAs injected intraoperatively with bupivacaine and epinephrine (one third pericapsular, two-thirds peri-incisional). The control group included 71 sequential TKAs. The study group had 32% (95% confidence interval, 11%-48%), or 195 mL, less drain output (P = .006). There were no statistically significant differences in the transfusion rate or bleeding indices. Control and study groups were comparable regarding tourniquet times, intraoperative soft-tissue releases, preoperative anticoagulant use, and overall postoperative complications. Our study demonstrated a statistically significant decrease in TKA postoperative drain output with intraoperative injection of bupivacaine with epinephrine. PMID- 19476179 TI - Proximal tibial fracture after patellar tendon autograft for ipsilateral ACL reconstruction. AB - Tibial plateau fracture after patellar tendon autograft is a documented complication of anterior cruciate ligament reconstruction. This case report describes a 24-year-old man who sustained this injury 7 years after anterior cruciate ligament (ACL) reconstruction. The patient tolerated open reduction and internal fixation of the tibial plateau. Tibial plateau fractures can occur relatively late in the recovery process after ACL reconstruction. Measures suggested to potentially reduce this complication include smaller osteotomies, use of allograft for patients with osteoporosis, and procuring the graft from the contralateral knee. PMID- 19476178 TI - Triad of cartilage restoration for unicompartmental arthritis treatment in young patients: meniscus allograft transplantation, cartilage repair and osteotomy. AB - Arthritis treatment in young patients remains a challenge. Joint replacement surgery offers excellent pain relief but is controversial with this age group because of long-term wear and loosening. Recently, biological reconstructive techniques have become available to improve traditional treatment methods such as osteotomies. We present our experience with a technique for combined meniscal transplantation, chondral repair, and osteotomy in 7 patients presenting with a constellation of meniscal deficiency, focal arthritis, and malalignment. Patients underwent concurrent or staged meniscal transplantation, cartilage repair, and osteotomy. Evaluation included the International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Short Form 12 and Lysholm scales. At average follow-up of 24 months, patients experienced significant improvements in the IKDC, Lysholm, and KOOS functional scores. Six of 7 patients were able to return to unrestricted activities; 1 patient experienced mild pain with high-impact activities. Combined treatment with meniscal transplantation, cartilage repair, and osteotomy demonstrated promising clinical results of unicompartmental arthritis treatment in young patients. PMID- 19476180 TI - [Cement plug embedded in the patella: a rare complication of total knee arthroplasty. AB - An unusual delayed complication of total knee arthroplasty involving the unresurfaced patella is described. The complication is due to the impaction of a loose cement plug used to seal the defect left by the femoral intramedullary alignment rod. The origin, presentation, and management are discussed. PMID- 19476181 TI - Anterior cruciate ligament graft placement. Foreword. PMID- 19476182 TI - Anterior cruciate ligament anatomy: a review of the anteromedial and posterolateral bundles. AB - Critical evaluations of anterior cruciate ligament (ACL) reconstruction failure modes have shown that the most common cause for failure is aberrant femoral tunnel placement. Regardless of the surgical reconstruction technique, it is imperative to have a thorough understanding of the anatomy and function of the anteromedial (AM) and posterolateral (PL) bundles of the native ACL to successfully restore the stability and motion of the injured knee. Similar to the observation that anatomic reduction is critical to successful fracture management, ACL reconstruction techniques must focus on restoring the normal anatomy of the ACL. This article reviews the anatomy of the AM and PL bundles of the ACL, including landmarks for identifying their femoral and tibial footprints. PMID- 19476183 TI - Transitioning to anatomic anterior cruciate ligament graft placement. AB - Anterior cruciate ligament (ACL) reconstruction techniques continue to improve. Recent biomechanical studies have found improved rotational stability as femoral tunnel placement becomes more horizontal and closer to the true ACL footprint. Clinical studies also correlate improved outcomes with these more anatomic reconstructions. This article reviews the transition from traditional to anatomic ACL reconstructions, as well as 3 techniques for achieving this: the modified transtibial technique, use of an accessory medial portal, and the retrograde drilling technique. PMID- 19476184 TI - Checkpoints for judging tunnel and anterior cruciate ligament graft placement. AB - This article examines how the relationship between sagittal and coronal anatomy, anterior cruciate ligament (ACL) graft dimensions, and tibial and femoral tunnel placement affects the posterior cruciate ligament (PCL) and roof impingement, and their undesirable clinical consequences of motion loss and instability. Based on these interrelationships, a variety of checkpoints are defined that can be used intraoperatively to determine whether placement of the tibial tunnel guidewire avoids PCL and roof impingement, and whether placement of the femoral tunnel guidewire avoids PCL impingement with either transtibial or transportal techniques. A simple, 3-dimensional tibial drill guide that consistently places the tibial tunnel correctly without PCL and roof impingement so the femoral tunnel, when drilled through the tibial tunnel, restores the normal tension pattern in the ACL graft also is described. Arthroscopic and radiographic checkpoints that assess the final placement of the ACL graft and tibial and femoral tunnels are discussed. PMID- 19476186 TI - Sharing the evidence, adding our clinical wisdom. PMID- 19476185 TI - Independent drilling of tibial and femoral tunnels in anterior cruciate ligament reconstruction. AB - Anterior cruciate ligament (ACL) reconstruction can be optimized when single bundle grafts are centered within the native ligament's tibial and femoral insertions. An understanding of ACL anatomy, including surgical landmarks for tunnel placement, is critical to accomplish this task. The best method for placing the femoral tunnel requires the independent, rather than a transtibial, drilling of the femoral tunnel. A good option for drilling the femoral tunnel is to drill through an anteromedial portal, but this method is challenging because it requires a high angle of knee flexion and visualization of the femoral insertion is limited during drilling. This review provides a rationale for independent tunnel drilling in ACL reconstruction, a method for identifying the insertional anatomy of the ACL, and a method for drilling the femoral tunnel through the anteromedial portal. PMID- 19476187 TI - Concerns about dedicated restorative care. PMID- 19476188 TI - The role of friends in predicting loneliness among older women living alone. AB - This study examines the role of friends in predicting loneliness among 53 women age 65 and older who live alone. It was hypothesized that friends would be more important in predicting loneliness for those participants who did not have family living in close proximity than for those who had family nearby. However, this was not the case: Self-reported close friends were important for women living alone, regardless of whether they had family living locally. Nurses may want to use these findings to encourage older women to make social connections, even if they live close to their family. PMID- 19476189 TI - Management of fever in older adults. AB - Few current standards exist for the identification and management of fever in older adults. Fever is one aspect of a controlled, complex febrile response that involves numerous physiological systems and must be distinguished from hyperthermia. Although most commonly identified with infection, numerous noninfectious etiologies exist. Fever is an adaptive response and is generally beneficial, especially in terms of the immunological response. Adverse consequences of fever are rare in older adults. Despite its metabolic costs, fever seldom requires treatment, except in certain patients who may not tolerate the stress. Controlling fever with antipyretic agents must be considered carefully, as the presence of fever may be helpful in guiding therapy, and antipyretic agents may have adverse effects. Recommendations are offered for identification and management of fever in older adults. PMID- 19476190 TI - Suicidal ideation, hardiness, and successful aging with HIV: considerations for nursing. AB - Several predictors of suicidal ideation found in older adults and adults with HIV are the same; synergistically, those aging with HIV may be at risk for suicidal ideation. Focusing on the concept of hardiness provides insight into mitigating suicidal ideation and accentuating successful aging with HIV. Some individuals may have hardy characteristics that counteract the detrimental effects of aging with HIV; others may require greater guidance to cope with the effects that lead to suicidal ideation. As these connections are examined, the concept of hardiness is examined in relation to aging with HIV. Implications for nursing are posited. PMID- 19476191 TI - A comparison of health promotion behaviors in rural and urban community-dwelling spousal caregivers. AB - Two decades of research describes the physical and mental stress experienced by caregivers, with little attention given to health promotion issues. The goal of this descriptive study was to identify and compare the health promotion behaviors (HPBs) used by older rural and urban women providing spousal care. Seventy-two women completed the Health Promoting Lifestyle Profile-II (HPLP-II) and a demographic survey. The most frequently reported HPBs related to interpersonal relations, spiritual growth, and stress management, while the least frequent related to physical activity. No significant differences existed on mean scores of the six subscales and overall HPLP-II of the rural and urban sample population. PMID- 19476192 TI - Use of multisensory environments in the home for people with dementia. AB - The purpose of this pilot study was to explore the feasibility and effectiveness of using multisensory environments (MSE) in the home of people with dementia. A qualitative research design was used, which included semi-structured interviews and self-rated caregiver observation checklists. Field notes and audio recorded interviews were transcribed for data analysis. Data were reduced and coded for theme identification. Positive and negative effects of the use of MSE in the home on the behaviors of the person with dementia, caregiver burden, and family interpersonal relationships were revealed. Overall, MSE was discovered to promote a relaxing and calm environment in the home, which helped the person with dementia attend more to their immediate surroundings, and to improve family interactions. Although the majority of caregivers reported they enjoyed the MSE, they acknowledged their disappointment in the MSE as not providing more caregiver respite. PMID- 19476193 TI - Steroid inhaler adherence, flu vaccine receipt, and race: associations with the quality of the parent-physician relationship for asthmatic children. AB - RATIONALE: Steroid inhaler adherence and influenza immunization rates are low for asthmatic minority children. OBJECTIVE: To examine associations between parents' adherence to administering their child's steroid inhaler, influenza vaccine receipt, and parental perceptions of the primary care experience. METHODS: In 2006 we interviewed parents of children aged 2-12 who had an asthma-related physician visit in 2004 and 2005 about steroid inhaler use and influenza vaccine receipt. Parents rated their child's doctor using the Primary Care Assessment Survey (PCAS). MEASUREMENT: Outcome variables were inhaler adherence and influenza vaccine receipt. Independent variables included PCAS scores, child health measures, parental personal and financial stress, and demographic variables. RESULTS: Children of inhaler-adherent parents were more likely to be immunized (OR, 2.94; p = .03). Black parents were less adherent to steroid use (OR, 0.37, p = .01) while nonblack/nonwhite children had lower vaccination rates (OR, 0.29, p = .02). Continuity of care was associated with better inhaler adherence (OR, 1.02, p = .01). Influenza immunization was associated with physician's knowledge of the child's medical history (OR, 1.02, p = .05), interpersonal skills (OR, 1.02, p = .03), and parental trust in the physician (OR, 1.03, p = .02). Minority parents gave lower ratings than white parents to their child's physician and office on characteristics associated with inhaler adherence and immunization. CONCLUSIONS: Minority parents of asthmatic children are less adherent to recommended asthma treatments and rate physicians lower on characteristics associated with adherence. Improving those characteristics may improve asthma outcomes for minority children. PMID- 19476194 TI - Trends in the prevalence and severity of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema. AB - The increase in prevalence of asthma and other allergic diatheses has rarely been documented in the developing sub-Saharan countries. We assessed time trends in symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema among children in Ibadan, Nigeria, with cross-sectional data from 2 International Study of Asthma and Allergies in Childhood questionnaire-based surveys conducted 7 years apart in 1995 and in 2001-2002. The prevalence of current wheeze increased nonsignificantly in the 6- to 7-year age group (4.8%-5.5%) and significantly in the 13- to 14-year age group (10.7%-13.0%) (p = .249 and p = .005, respectively). The 12-month prevalence of allergic rhinoconjuctivitis decreased insignificantly in the 6- to 7-year age group (p = .833) but significantly in the 13- to 14-year age group (p = .001), while the diagnosis of atopic eczema decreased in both age groups. The current findings suggest that the symptoms of asthma have only increased significantly in the Nigerian adolescents. PMID- 19476195 TI - Assessing childhood obesity programs in low-socioeconomic and diverse communities. AB - BACKGROUND: Childhood obesity disproportionately affects low-socioeconomic and diverse communities. After a national children's health care quality organization announced a request for programs addressing the prevention and treatment of childhood obesity, 80 programs were received. The objective of this study was to identify a best practice for addressing childhood obesity in low-socioeconomic and diverse communities. METHODS: A secondary analysis of the 80 programs was conducted in spring 2007 using a framework developed after a mini literature review using PubMed and Google, a review of the recommendations from the 1998 national childhood obesity expert committee, and 5 semistructured interviews with childhood obesity key informants. RESULTS: The key informants unanimously recommended that obesity reduction programs in low-socioeconomic and diverse communities should combine 4 themes: lifestyle changes, family-centeredness, prevention, and early community involvement. These 4 themes were combined in 50% of the 80 programs. CONCLUSIONS: An evidence-based best practice for reducing childhood obesity in low-socioeconomic and diverse communities could not be identified utilizing the 4 themes recommended by the key informants. Preliminary data suggest that 1 academic program may offer promise for addressing childhood obesity in low-socioeconomic and diverse communities and improved data collection. PMID- 19476196 TI - Disparities in diabetic retinopathy screening and disease for racial and ethnic minority populations--a literature review. AB - Diabetic retinopathy is the leading cause of blindness in the United States. This sight-threatening complication of diabetes mellitus disproportionately affects racial and ethnic minority populations. Tight glycemic control and routine eye screening can diminish the public health impact of this devastating condition in minority communities. However, racial and ethnic minority patients are more likely to have poorer glycemic control and are less likely to be screened for diabetic retinopathy than their white counterparts. Patient, provider, and health care system factors play a role in these disparities. While public health interventions are necessary on a large scale to preserve vision in minority communities, it is also essential that individual health care providers better understand the impact of diabetic retinopathy on minority communities and the available interventions to reduce its impact. Maximizing their efforts to improve diabetes-related vision care for their racial and ethnic minority patients can lead to a decrease in diabetic retinopathy disparities. PMID- 19476197 TI - Why some adolescents lose weight and others do not: a qualitative study. AB - OBJECTIVES: Understanding the experiences of overweight adolescents who have lost weight may be useful in the creation of effective weight loss programs. Our objective was to identify differences between the experiences of overweight, inner-city adolescents who lost weight compared to adolescents who gained weight over time. METHODS: A qualitative study of a convenience sample of overweight inner-city adolescents, comparing those whose body mass index (BMI)-for-age decreased to those whose BMI-for-age increased, was done over a period of 2 years. Focus groups and in-depth interviews were analyzed by the constant comparative method; frequencies of thematic responses were compared. RESULTS: Adolescents in both groups had poor diets, had similar rates of eating with parents, had complex effects of monetary constraints, had ambivalence about being overweight, and lived in unsafe neighborhoods. Weight-losing adolescents were more likely to describe a transformative experience, which changed their view of themselves in the world with regard to weight and activity; to engage in intense, daily exercise; and to have family members who supported healthy dietary behavior. CONCLUSION: Transformative experiences, intense daily exercise, and family support appeared to be critical elements for weight reduction in inner city adolescents. This information may guide the development of weight loss strategies. PMID- 19476198 TI - Predictors of enrollment in a smoking cessation clinical trial after eligibility screening. AB - PURPOSE: A fraction of smokers considered eligible for pharmacotherapy treatment trials for nicotine dependence enrolled. Little is known about smokers not enrolling in a treatment trial or how these smokers differ from those who have enrolled. PROCEDURES: We screened 2257 individuals for a smoking cessation trial involving behavioral counseling and a novel medication. FINDINGS: Of those screened, 33% of callers were eligible for enrollment (N=753). Of those eligible for the trial, 37% attended the subsequent enrollment session (N=282). We compared the 282 attendees to the 471 smokers who were eligible for the trial but did not attend. Logistic regression indicated that African American smokers were about half as likely to enroll in the trial (odds ratio [OR], 0.55; 95% CI, 0.36 0.84); for every year increase in age, participants were 4% more likely to enroll (OR, 1.04; 95% CI, 1.02-1.06); and participants who were motivated to enroll in the trial for financial incentives were 42% less likely to enroll in the trial (OR, 0.58; 95% CI, 0.45-0.76). CONCLUSIONS: These findings suggest the need to devise and test recruitment strategies directed toward African Americans and younger smokers to increase enrollment among eligible smokers to smoking cessation treatment trials. PMID- 19476199 TI - Racial disparities in mortality among infants with Dandy-Walker syndrome. AB - BACKGROUND: Congenital malformations are the major cause of infant mortality in the United States, but their contribution to overall racial disparity--a major public health concern--is poorly understood. We sought to estimate the contribution of a congenitally acquired central nervous system lesion, Dandy Walker Syndrome (DWS), to black-white disparity in infant mortality. METHODS: Data were obtained from the New York State Congenital Malformations Registry, an ongoing population-based validated surveillance system. We compared black to white infants with respect to infant, neonatal, and postneonatal mortality using Cox proportional hazards regression models. RESULTS: A total of 196 live-born neonates were diagnosed with DWS in the state from 1992 to 2005 inclusive. Of these, 53 were non-Hispanic black and 76 were non-Hispanic white. Neonatal mortality was similar for non-Hispanic blacks and non-Hispanic whites (adjusted hazards ratio [AHR], 1.42; 95% CI, 0.52-3.82), but non-Hispanic blacks had an 8 fold increased risk for postneonatal mortality (AHR, 8.26; 95% CI, 2.08-32.72). Adjustment for fetal growth and other maternal and infant characteristics resulted in a 10-fold increased risk of mortality for non-Hispanic black infants as compared to non-Hispanic whites. By contrast, adjustment for preterm birth attenuated the risk, but non-Hispanic black infants were still more than 6 times as likely to die during the postneonatal period than non-Hispanic whites (AHR, 6.36, 95% CI, 1.52-26.60). CONCLUSION: DWS has one of the largest black-white disparities in postneonatal survival. This underscores the importance of evaluating racial disparities in infant mortality by specific conditions in order to formulate targeted interventions to reduce disparities. PMID- 19476200 TI - Gastrointestinal stromal tumor of the esophagus. AB - Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms that account for 0.2% of all GI neoplasms. We report a case of a 62-year-old male with a large esophageal GIST, and discuss the pathophysiology of the disease and the current management principles. This case is noteworthy because it documents a rare lesion in the esophagus that presents like other neoplastic diseases in this organ that usually carry a poor prognosis. An aggressive approach (e.g., more radical surgery, radiotherapy, and chemotherapy) might have been pondered based purely on the size of the lesion in this patient. It is important that primary care physicians and surgeons be aware of the possibility of the presence of this potentially curable lesion so as to avoid overtreatment. PMID- 19476201 TI - E. Anthony Rankin, MD: President of the American Academy of Orthopaedic Surgeons. Interviewed by George Anthony Dawson. PMID- 19476202 TI - Challenges of utilizing immunostains to facilitate the diagnosis and management of metastatic adenocarcinoma. PMID- 19476203 TI - A call to action against asthma. PMID- 19476204 TI - Extracellular matrix in pancreatic islets: relevance to scaffold design and transplantation. AB - Intrahepatic islet transplantation provides a potentially more benign alternative to pancreatic transplantation. However, islet transplants are associated with limited engraftment potential. This inefficiency is likely at least partially attributable to the isolation process, which removes islets from their native environment. Isolation not only disrupts the internal vascularization and innervation of islets, but also fundamentally changes interactions between islet cells and macromolecules of the extracellular matrix (ECM). Signaling interactions between islet cells and ECM are known to regulate multiple aspects of islet physiology, including survival, proliferation, and insulin secretion. Although it is highly likely that disruptions to these interactions during isolation significantly affect transplant outcomes, the true implications of these conditions are not well understood. The following article reviews current understandings and uncertainties in islet-ECM interactions and explains their potential impact on posttransplant engraftment. Topics covered include matrix and receptor compositions in native islets, effects of isolation and culture on islet ECM interactions, and potential for postisolation restoration of islet-ECM interactions. Greater understanding in these areas may help to reduce isolation and transplantation stresses and improve islet engraftment. PMID- 19476205 TI - Toward improving human islet isolation from younger donors: rescue purification is efficient for trapped islets. AB - Several reports suggest that islets isolated from younger donor pancreata are of better quality for clinical islet transplantation. The relative inefficiency of the continuous gradient purification process (CGP) is one of the major obstacles to the utilization of these younger donor pancreata. This study demonstrates the benefits of utilizing an additional purification step, rescue gradient purification (RGP), to recover trapped islets and examines the possible superiority of these rescued islets. Seventy-three human islet isolations purified by RGP following CGP were divided into two groups based on age, and the isolation results were retrospectively analyzed (group I: age < or = 40, group II: age > 40). The quality of islets from both CGP and RGP were assessed by beta cell fractional viability (beta FV) and ADP/ATP ratio. Significant increases in the percent islet recovery from RGP and the percent trapped islets in group I compared to group II were observed. Donor age correlated negatively to the percent islets recovered from RGP (R = 0.440) and to the percent of trapped islets (R = 0.511). RGP islets had higher beta FV and better ADP/ATP ratio compared to CGP islets. In conclusion, RGP improved the efficiency in the purification of trapped islets, which often come from younger donor pancreata. The better quality of beta-cells in RGP islets encourages us to perform RGP, considering the higher quality as well as the quantity of remaining islets. PMID- 19476206 TI - Beneficial role of pancreatic microenvironment for angiogenesis in transplanted pancreatic islets. AB - Pancreatic islets implanted heterotopically (i.e., into the kidney, spleen, or liver) become poorly revascularized following transplantation. We hypothesized that islets implanted into the pancreas would become better revascularized. Islets isolated from transgenic mice expressing enhanced yellow fluorescent protein (EYFP) in all somatic cells were cultured before they were implanted into the pancreas or beneath the renal capsule of athymic mice. Vascular density was evaluated in histological sections 1 month posttransplantation. EYFP was used as reporter for the transgene to identify the transplanted islets. Islet endothelial cells were visualized by staining with the lectin Bandeiraea simplicifolia (BS 1). Capillary numbers in intrapancreatically implanted islets were only slightly lower than those counted in endogenous islets, whereas islets implanted beneath the renal capsule had a markedly lower vascular density. In order to determine if this high graft vascular density at the intrapancreatic site reflected expansion of remnant donor endothelial cells or increased ingrowth of blood vessels from the host, also islets from Tie2-green fluorescent protein (GFP) mice (i.e., islets with fluorescent endothelial cells) were transplanted into the pancreas or beneath the renal capsule of athymic mice. These islet grafts revealed that the new vascular structures formed in the islet grafts contained very few GFP positive cells, and thus mainly were of recipient origin. The reason(s) for the much better ingrowth of blood vessels at the intrapancreatic site merits further studies, because this may help us form strategies to overcome the barrier for ingrowth of host vessels also into islets in heterotopic implantation sites. PMID- 19476207 TI - The effect of composite pig islet-human endothelial cell grafts on the instant blood-mediated inflammatory reaction. AB - Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in portal vein islet transplantation. Endothelial cells are known to protect against complement-mediated lysis and activation of coagulation. We tested composite pig islet-human endothelial cell grafts as a strategy to overcome IBMIR. Porcine islets were cocultured with human endothelial cells in specially modified culture medium composed of M199 and M200 for 1-9 days. A positive control group, negative control group, and the endothelial cell-coated group were examined with an in vitro tubing loop assay using human blood. The endothelial cell-coated group was subdivided and analyzed by degree of surface coverage by endothelial cells (< or = 50% vs. > 50%) or coculture time (< 5 days vs. > or = 5 days). Platelet consumption and complement and coagulation activation were assessed by platelet count, C3a, and thrombin-antithrombin complex (TAT), respectively. After 60-min incubation in human blood, the endothelial cell-coated group showed platelet consumption inhibition and low C3a and TAT assay results compared to uncoated controls. When the endothelial cell-coated group was subdivided by degree of surface coverage, the < or = 50% coated group showed less platelet consumption and less activation of complement and coagulation compared with the positive control (uncoated) group. On analysis by coculture time, only the subgroup cocultured for < 5 days showed the same protective effect. Human endothelial cell coated pig islets, especially the partially coated and short-term cocultured pig islet-human endothelial cell composites, reduced all components of IBMIR. If the optimal endothelial cell-islet coculture method could be identified, human endothelial cell coating of pig islets would offer new strategies to improve xenogenic islet transplantation outcomes. PMID- 19476208 TI - Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development. AB - Embryonic stem (ES) cells are a potential source for treatment of spinal cord injury (SCI). Although one of the main problems of ES cell-based cell therapy is tumor formation, there is no ideal method to suppress tumor development. In this study, we examined whether transplantation with bone marrow stromal cells (BMSCs) prevented tumor formation in SCI model mice that received ES cell-derived grafts containing both undifferentiated ES cells and neural stem cells. Embryoid bodies (EBs) formed in 4-day hanging drop cultures were treated with retinoic acid (RA) at a low concentration of 5 x 10(-9) M for 4 days, in order to allow some of the ES cells to remain in an undifferentiated state. RA-treated EBs were enzymatically digested into single cells and used as ES cell-derived graft cells. Mice transplanted with ES cell-derived graft cells alone developed tumors at the grafted site and behavioral improvement ceased after day 21. In contrast, no tumor development was observed in mice cotransplanted with BMSCs, which also showed sustained behavioral improvement. In vitro results demonstrated the disappearance of SSEA-1 expression in cytochemical examinations, as well as attenuated mRNA expressions of the undifferentiated markers Oct3/4, Utf1, Nanog, Sox2, and ERas by RT-PCR in RA-treated EBs cocultured with BMSCs. In addition, MAP2-immunopositive cells appeared in the EBs cocultured with BMSCs. Furthermore, the synthesis of NGF, GDNF, and BDNF was confirmed in cultured BMSCs, while immunohistochemical examinations demonstrated the survival of BMSCs and their maintained ability of neurotrophic factor production at the grafted site for up to 5 weeks after transplantation. These results suggest that BMSCs induce undifferentiated ES cells to differentiate into a neuronal lineage by neurotrophic factor production, resulting in suppression of tumor formation. Cotransplantation of BMSCs with ES cell-derived graft cells may be useful for preventing the development of ES cell-derived tumors. PMID- 19476210 TI - Noninvasive imaging of liver repopulation following hepatocyte transplantation. AB - Near infrared fluorescence (NIRF) optical imaging is a technique particularly powerful when studying in vivo processes at the molecular level in preclinical animal models. We recently demonstrated liver irradiation under the additional stimulus of partial hepatectomy as being an effective primer in the rat liver repopulation model based on hepatocyte transplantation. The purpose of this study was to assess optical imaging and the feasibility of donor cell expansion tracking in vivo using a fluorescent probe. Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with irradiation. Four days later, a partial hepatectomy was performed and wild-type (DPPIV+) hepatocytes were transplanted into recipient livers via the spleen. Repopulation by transplanted DPPIV+ hepatocytes was detected in vivo with Cy5.5-conjugated DPPIV antibody using the eXplore Optix System (GE HealthCare). Results were compared with nontransplanted control animals and transplanted animals receiving nonspecific antibody. Optical imaging detected Cy5.5-specific fluorescence in the liver region of the transplanted animals, increasing in intensity with time, representing extensive host liver repopulation within 16 weeks following transplantation. A general pattern of donor cell multiplication emerged, with an initially accelerating growth curve and later plateau phase. In contrast, no specific fluorescence was detected in the control groups. Comparison with ex vivo immunofluorescence staining of liver sections confirmed the optical imaging results. Optical imaging constitutes a potent method of assessing the longitudinal kinetics of liver repopulation in the rat transplantation model. Our results provide a basis for the future development of clinical protocols for suitable fluorescent dyes and imaging technologies. PMID- 19476211 TI - Wheat proteins enhance stability and function of adhesion molecules in cryopreserved hepatocytes. AB - Cryopreserved hepatocytes with good hepatospecific functions upon thawing are important for clinical transplantation and for in vitro drug toxicity testing. However, cryopreservation reduces viability and certain hepatospecific functions, but the most pronounced change is diminished attachment efficiency of hepatocytes. Adhesion of cells to the extracellular matrix and cell-cell contacts are crucial for many aspects of cellular function. These processes are partly mediated and controlled by cellular adhesion molecules. The mechanisms responsible for reduced attachment efficiency of cryopreserved hepatocytes are not well understood. To address this question, we investigated the effect of a new cryopreservation procedure, using wheat proteins (WPs) or mixtures of recombinant forms of wheat freezing tolerance-associated proteins, on the stability of three important adhesion molecules (beta1-integrin, E-cadherin, and beta-catenin). Immunoblot analyses revealed that the levels of beta1-integrin, E cadherin, and beta-catenin were much lower in cryopreserved rat hepatocytes, when compared to fresh cells. Protein expression of the adhesion molecules was generally lower in cells cryopreserved with DMSO, compared to WPs. Moreover, the stability of the adhesion molecules was not affected by cryopreservation to the same degree, with more pronounced decreases occurring for beta1-integrin (62-74%) > beta-catenin (51-58%) > E-cadherin (21-37%). However, when hepatocytes were cryopreserved with partially purified WPs (SulWPE, AcWPE) or with mixtures of recombinant wheat proteins, there was a clear protective effect against the loss of protein expression of beta1-integrin, E-cadherin, and beta-catenin. Protein expression was only 10-20% lower than that observed in fresh hepatocytes. These findings clearly demonstrate that WPs, and more particularly, partially purified WPs and recombinant wheat proteins, were more efficient for cryopreservation of rat hepatocytes by maintaining good expression of these adhesion molecules. These promising results could lead to a new and improved cryopreservation technology for applications such as clinical transplantation of hepatocytes. PMID- 19476209 TI - Retentive multipotency of adult dorsal root ganglia stem cells. AB - Preservation of neural stem cells (NSCs) in the adult peripheral nervous system (PNS) has recently been confirmed. However, it is not clear whether peripheral NSCs possess predestined, bona fide phenotypes or a response to innate developmental cues. In this study, we first demonstrated the longevity, multipotency, and high fidelity of sensory features of postmigrating adult dorsal root ganglia (aDRG) stem cells. Derived from aDRG and after 4-5 years in culture without dissociating, the aDRG NSCs were found capable of proliferation, expressing neuroepithelial, neuronal, and glial markers. Remarkably, these aDRG NSCs expressed sensory neuronal markers vesicular glutamate transporter 2 (VGluT2 -glutamate terminals), transient receptor potential vanilloid 1 (TrpV1--capsaicin sensitive), phosphorylated 200 kDa neurofilaments (pNF200--capsaicin insensitive, myelinated), and the serotonin transporter (5-HTT), which normally is transiently expressed in developing DRG. Furthermore, in response to neurotrophins, the aDRG NSCs enhanced TrpV1 expression upon exposure to nerve growth factor (NGF), but not to brain-derived neurotrophic factor (BDNF). On the contrary, BDNF increased the expression of NeuN. Third, the characterization of aDRG NSCs was demonstrated by transplantation of red fluorescent-expressing aDRG NSCs into injured spinal cord. These cells expressed nestin, Hu, and beta-III-tubulin (immature neuronal markers), GFAP (astrocyte marker) as well as sensory neural marker TrpV1 (capsaicin sensitive) and pNF200 (mature, capsaicin insensitive, myelinated). Our results demonstrated that the postmigrating neural crest adult DRG stem cells not only preserved their multipotency but also were retentive in sensory potency despite the age and long-term ex vivo status. PMID- 19476213 TI - Improved survival of fulminant liver failure by transplantation of microencapsulated cryopreserved porcine hepatocytes in mice. AB - The aim of this study was to establish hepatocyte isolation in pigs, and to evaluate function of isolated hepatocytes after encapsulation, cryopreservation, and transplantation (Tx) in a mouse model of fulminant liver failure (FLF). After isolation, porcine hepatocytes were microencapsulated with alginate-poly-L-Lysine alginate membranes and cryopreserved. In vitro, albumin production of free and encapsulated hepatocytes were measured by enzyme linked-immunoadsorbent assay. In vivo, encapsulated hepatocytes were transplanted into different groups of mice with FLF and the following experimental groups were performed: group 1, Tx of empty capsules; group 2, Tx of free primary porcine hepatocytes; group 3, Tx of fresh encapsulated porcine hepatocytes; group 4, Tx of cryopreserved encapsulated porcine hepatocytes. In vitro, fresh or cryopreserved encapsulated porcine hepatocytes showed a continuous decreasing metabolic function over 1 week (albumin and urea synthesis, drug catabolism). In vivo, groups 1 and 2 showed similar survival (18% and 25%, respectively, p > 0.05). In groups 3 and 4, Tx of fresh or cryopreserved encapsulated porcine hepatocytes significantly increased survival rate to 75% and 68%, respectively (p < 0.05). Primary porcine hepatocytes maintained metabolic functions after encapsulation and cryopreservation. In mice with FLF, Tx of encapsulated xenogeneic hepatocytes significantly improved survival. These results indicate that porcine hepatocytes can successfully be isolated, encapsulated, stored using cryopreservation, and transplanted into xenogeneic recipients with liver failure and sustain liver metabolic functions. PMID- 19476212 TI - Suppression of carbon tetrachloride-induced liver fibrosis by transplantation of a clonal mesenchymal stem cell line derived from rat bone marrow. AB - Transplantation of hepatocytes or bone marrow-derived cells has been shown to ameliorate liver fibrosis in animal models, but no direct comparison of relative efficiency has been made. The aim of this study was to compare the efficiency of a bone marrow-derived clonal mesenchymal stem cell line established by us (rBM25/S3) with that of its adipogenic or hepatogenic differentiation derivative for suppression of rat liver fibrosis. After induction of differentiation of rBM25/S3 cells into adipogenic or hepatogenic cells in culture, we intrasplenically transplanted the three types of cells into rats (3 x 10(7) cells/rat) before and 4 weeks after initiation of carbon tetrachloride treatment (1 ml/kg body weight twice a week for 8 weeks) to induce liver fibrosis. Undifferentiated rBM25/S3 cells were the most effective for suppression of liver fibrosis, followed by the adipogenic cells and hepatogenic cells. Expression levels of MMP-2 and MMP-9 were also highest in undifferentiated rBM25/S3 cells. These results indicate that bone marrow-derived clonal mesenchymal stem cell lines are useful for further mechanistic studies on cell-mediated suppression of liver fibrosis and that such cell lines will provide information on an appropriate cell source for transplantation therapy for cirrhosis. PMID- 19476214 TI - Empirical performance of optimal Bayesian adaptive estimation. AB - Simulation studies have shown how Bayesian adaptive estimation methods should be set up for optimal performance. We assessed the extent to which these results hold up for human observers, who are more subject to failure than simulation subjects. Discrimination and detection experiments with two-alternative forced choice (2AFC) tasks were used for that purpose. Forty estimates of the point of subjective equality (PSE, or the 50% correct point on the psychometric function for discrimination) and 32 estimates of detection threshold (the 80% correct point on the psychometric function for detection) were taken for each of four observers with the optimal Bayesian method, while data for fitting the psychometric function psi were gathered concurrently with an adaptive method of constant stimuli governed by fixed-step-size staircases. The estimated parameters of the psychometric function served as a criterion for comparison. In the discrimination task, PSEs for each observer were distributed around the independently estimated 50% correct point on psi and their variability was occasionally minimally larger than simulation results indicated it should be. In the detection task, the distribution of threshold estimates was consistently above the independently estimated 80% correct point on psi and their variability was as expected from simulations. A close analysis of these results suggests that the optimal Bayesian method is affected by growing inattention or fatigue in detection tasks (factors that are not considered in simulations), and limits the practical applicability of Bayesian estimation of detection thresholds. PMID- 19476215 TI - The effects of agonists of ionotropic GABA(A) and metabotropic GABA(B) receptors on learning. AB - The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABA(A) and metabotropic GABA(B) receptors and 2) gaboxadol a selective agonist of ionotropic GABA(A) receptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABA(B) receptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABA(A) and GABA(B) receptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes. PMID- 19476216 TI - Hemispheric differences for global and local processing: effect of stimulus size and sparsity. AB - The present experiment was designed to assess the hemispheric differences for global and local processing in healthy participants under different conditions of stimuli visibility, by means of varying the size and sparsity. Three different sizes and three different matrixes of hierarchical stimuli were introduced. Stimuli consisted of incomplete squares with one side missing. Participants were asked to carry out an orientation classification task (left/right), indicating the orientation of the square opening either at global or local levels. The results do not support the hemispheric differences for global and local processing, showing the same efficiency of right and left hemispheres for analyzing global and local information. Nevertheless, other results found are consistent with the hypothesis of right hemisphere superiority under degraded stimulus conditions. PMID- 19476217 TI - Electroencephalographic evidence on the strategies of adaptation to the factors of monotony. AB - In a series of studies, in which 19 apparently healthy male volunteers participated, on the basis of a comparative analysis of the bioelectric brain activity and work performance, it is shown that two strategies of adaptation to the factors of monotony are possible. One of them is based on the maintenance of a high quality of activity even at the price of a considerable reduction in the functional state of the brain; the second is based on the maintenance of the functional status of the brain even at the expense of the short-term loss of control over realizable performance. The factor conditioning the long term inability to support continual high quality of performance under the conditions of monotony is a high lability in nervous processes. The resistance to the effects of the factors of monotony is connected, on the other hand, with the low lability of nervous processes with a certain predominance of excitatory processes over inhibiting processes. The electrographic correlates of the development of the state of monotony represent an increase in the EEG of an alert person of the slow spectra (theta and alpha), and also beta-2 waves, as well as a reduction in the intrahemispheric coherence of alpha-waves. These results can be used for the development of control systems for the state of the operators who work in conditions of monotony (pilots, the operators of electric trains, the operators of power plants, including atomic power plants, and others), as well as in the occupational selection of individuals for jobs involving work under such conditions. PMID- 19476218 TI - Facial affect recognition deficit as a marker of genetic vulnerability to schizophrenia. AB - The aim of this study was to investigate the possibility that affect recognition impairments are associated with genetic liability to schizophrenia. In a group of 55 unaffected relatives of schizophrenia patients (parents and siblings) we examined the capacity to detect facially expressed emotions and its relationship to schizotypal personality, neurocognitive functioning, and the subject's actual emotional state. The relatives were compared with 103 schizophrenia patients and 99 healthy subjects without any family history of psychoses. Emotional stimuli were nine black-and-white photos of actors, who portrayed six basic emotions as well as interest, contempt, and shame. The results evidenced the affect recognition deficit in relatives, though milder than that in patients themselves. No correlation between the deficit and schizotypal personality measured with SPQ was detected in the group of relatives. Neither cognitive functioning, including attention, verbal memory and linguistic ability, nor actual emotional states accounted for their affect recognition impairments. The results suggest that the facial affect recognition deficit in schizophrenia may be related to genetic predisposition to the disorder and may serve as an endophenotype in molecular genetic studies. PMID- 19476219 TI - The role of connectives in the comprehension of spontaneous spoken discourse. AB - The role of connectives in the comprehension of spontaneous spoken discourse has been investigated by testing the effect of the connective 'but' in the realization of causal inferences and the integration of adjacent statements. The role of this connective in the realization of causal inferences has been tested through a judgment task. The role of 'but' in the integration of the adjacent statements has been tested through a word monitoring task. The presence of the connective resulted in shorter reaction times for the realization of causal inferences in the judgment task, but it did not result in shorter reaction times for the integration of adjacent statements, as measured by the word monitoring task. These results suggest that listeners are able to make use of connectives to help them create and decide on the existence of causal connections, but not to process and recognize the surface form of the second statement of the pair. PMID- 19476220 TI - A longitudinal research on the development of emotional autonomy during adolescence. AB - The purpose of the present paper was to study the development of emotional autonomy through adolescence analysing its association with family relationships. The development of emotional autonomy involves an increase in adolescents' subjective sense of his or her independence, especially in relation to parents. From some scholars emotional autonomy is a normative manifestation of the detachment process from parents, however, others point out that detachment from parental ties is not the norm, so high level of adolescent emotional autonomy is the consequence of negative family relationships. In our study a sample of 101 adolescents were followed for 5 years, from early to middle adolescence, and completed questionnaires to measure their emotional autonomy and the quality of their family relationships. Our results showed that over the course of adolescence some dimensions of emotional autonomy increase, meanwhile others decrease, so the global level of emotional autonomy global level remains stable. On the other hand, emotional autonomy is associated with negative family relationships, so emotional autonomy, more than a necessary process to become adult, could be indicating an insecure attachment to parents. PMID- 19476221 TI - Are women more empathetic than men? A longitudinal study in adolescence. AB - Since the 1970s there has been a growing interest in analysing sex differences in psychological variables. Empirical studies and meta-analyses have contributed evidence on the differences between male and female individuals. More recently, the gender similarities hypothesis has supported the similarity of men and women in most psychological variables. This study contributes information on women's greater empathic disposition in comparison with men by means of a longitudinal design in an adolescent population. 505 male and female adolescents aged between 13 and 16 years were evaluated at two different moments (grade 2 and grade 3, lower secondary education). They completed the Index of Empathy for Children and Adolescents by Bryant and the Interpersonal Reactivity Index by Davis. The results confirm a greater empathic response in females than in males of the same age, differences growing with age. The sizes of the effect estimated in the second evaluation (average age 14 years) are large for emotional empathy and medium for cognitive empathy. PMID- 19476222 TI - Early predictors of reading in three groups of native Spanish speakers: Spaniards, Gypsies, and Latin Americans. AB - The main purpose of the study reported here was to examine the early linguistic predictors of reading (e.g., Knowledge About Print, Listening Comprehension, Receptive Vocabulary, Rapid Naming of Objects and Letters, and Phonological Awareness), for a sample of 77 Spaniards, 48 Latinos, and 30 Gypsies kindergartens (mean age = 5 years 9 months) living in Spain. The relative contribution of ethnic background, neighbourhood socioeconomic status (SES), age, and gender was assessed. Findings revealed that ethnic background, neighborhood SES, and age differentially predicted children's pre-literacy skills. The implications of these results for understanding the role played by these demographic and socio-cultural variables in alphabetic literacy acquisition are discussed. The second purpose of this study was to add to the growing literature on the nature of reading challenges in children who are learning to read a transparent orthography-Spanish. Cross-linguistic research between different subtypes of readers will add to understand the impact of language characteristics in reading acquisition. Finally, the present study suggested that early assessment of pre-literacy skills can be a highly effective way to determine the instructional needs of students who are at risk for reading failure before formal reading instruction begins. PMID- 19476223 TI - Academic goals and learning quality in higher education students. AB - In this paper, the relations between academic goals and various indicators that define the quality of the learning process are analyzed. The purpose was to determine to what extent high, moderate, or low levels of academic goals were positively or negatively related to effort regulation, the value assigned to academic tasks, meta-cognitive self-regulation, self-efficacy, beliefs about learning control, and management of time and study environment. The investigation was carried out with a sample of 632 university students (70% female and 30% male) and mean age of 21.22 (SD=2.2).The results show that learning goals, or task orientation, are positively related to all the indictors of learning quality considered herein. Although for other kinds of goals-work-avoidance goals, performance-approach goals, and performance-avoidance goals-significant relations were not found with all the indicators, there was a similar tendency of significant results in all cases; the higher the levels of these goals, the lower the levels of the indicators of learning quality. PMID- 19476225 TI - Academic procrastination: associations with personal, school, and family variables. AB - Procrastination is a common behavior, mainly in school settings. Only a few studies have analyzed the associations of academic procrastination with students' personal and family variables. In the present work, we analyzed the impact of socio-personal variables (e.g., parents' education, number of siblings, school grade level, and underachievement) on students' academic procrastination profiles. Two independent samples of 580 and 809 seventh to ninth graders, students attending the last three years of Portuguese Compulsory Education, have been taken. The findings, similar in both studies, reveal that procrastination decreases when the parents' education is higher, but it increases along with the number of siblings, the grade level, and the underachievement. The results are discussed in view of the findings of previous research. The implications for educational practice are also analyzed. PMID- 19476224 TI - Parental influences on students' self-concept, task value beliefs, and achievement in science. AB - The aim of this study was twofold: firstly, to investigate the grade level (elementary and middle school) and gender effect on students' motivation in science (perceived academic science self-concept and task value) and perceived family involvement, and secondly to examine the relationship among family environment variables (fathers' educational level, mothers' educational level, and perceived family involvement), motivation, gender and science achievement in elementary and middle schools. Multivariate Analysis of Variance (MANOVA) showed that elementary school students have more positive science self-concept and task value beliefs compared to middle school students. Moreover, elementary school students appeared to perceive more family involvement in their schooling. Path analyses also suggested that family involvement was directly linked to elementary school students' task value and achievement. Also, in elementary school level, significant relationships were found among father educational level, science self concept, task value and science achievement. On the other hand, in middle school level, family involvement, father educational level, and mother educational level were positively related to students' task value which is directly linked to students' science achievement. Moreover, mother educational level contributed to science achievement through its effect on self-concept. PMID- 19476227 TI - Coach autonomy support and quality of sport engagement in young soccer players. AB - Based on the self-determination theory (Ryan & Deci, 2000), this study tested a model of the assumed sequential relationships between perceived autonomy support, psychological need satisfaction, self-determined motivation, and enjoyment/boredom. The hypothesized mediational roles of psychological need satisfaction and self-determined motivation were also studied. In a sample of 370 young male soccer players, path analysis results offered support for the proposed model. Total mediation was supported in the case of the psychological need satisfaction in the relationship between autonomy support and self-determined motivation, and partial mediation for self-determined motivation in the links between psychological need satisfaction and enjoyment (positive) and boredom (negative). Implications of autonomy-supportive behaviors provided by coaches for the quality of sport involvement among young athletes are discussed. PMID- 19476226 TI - Determinants of leisure-time physical activity and future intention to practice in Spanish college students. AB - Few studies analyze determinants and patterns of physical activity among college students, so it has not been possible to carry out effective interventions to promote this practice. The aim of this study was to analyze the associations between some personal, social, and environmental determinants, practice of physical activity and future intention to practice in a sample of 639 university students (321 men and 318 women), mean age 21.43 years (+/- 2.78). Physical fitness self-perception, physical activity history, and coach's support to practice physical activity have a direct effect on the practice of physical activity and an indirect effect on future intention to practice, both in men and women. The practice of physical activity has also a direct effect on future intention to practice. Likewise, the participation in sport competitions predicts practice of physical activity and future intention in men, whereas being a member of a sports club predicts practice and future intention in women. PMID- 19476228 TI - Self-concept, self-esteem, personality traits and psychopathological symptoms in adolescents with and without visual impairment. AB - The purpose of this study was to analyze self-concept, self-esteem, and other personality traits and psychopathological symptoms in subjects with and without visual impairment. The sample was made up of 90 participants aged 12 to 17: 61 with no impairment and 29 with visual impairment. The ANOVA showed that there were no significant differences in self-concept and self-esteem in the samples, but the visually impaired adolescents scored significantly higher in various psychopathological symptoms as well as in their capacity for kind behavior. The ANOVA revealed no gender differences in any variables in adolescents without visual impairment. However, women with visual impairment scored lower in self esteem and higher in various psychopathological symptoms. Pearson coefficients revealed negative relations between self-concept/self-esteem and all the psychopathological symptoms, and neuroticism, as well as a positive relation with extraversion. Low psychoticism, high extraversion, and low hostility were identified as predictors of high self-concept. PMID- 19476229 TI - Anxiety and depression in mothers of preterm infants and psychological intervention during hospitalization in neonatal ICU. AB - The objective of this study was to evaluate and compare symptoms of anxiety and depression before and after psychological intervention in mothers of babies born preterm with very low birth weight, hospitalized in the Neonatal Intensive Care Unit. Fifty nine mothers, without psychiatric antecedents, were distributed into two groups according to the type of psychological intervention received. Group G1 included 36 mothers who received routine psychological treatment associated with initial structured intake using support materials (video and guidance manual). Group G2 included 23 mothers who received routine psychological intervention without support material. The STAI and BDI, respectively, were used to evaluate maternal indicators of anxiety and depression. The results revealed that both groups showed a reduction in levels of state or trait anxiety and depression after psychological intervention and discharge of the baby from the hospital. In regard to the emotional symptoms at a clinical level, a statistically significant reduction in the level of state-anxiety was verified in G1. The findings confirmed the need for psychological support for mothers of preterm infants and the use of materials focusing on prematurity for reduction of the situational anxiety on a clinical level. PMID- 19476230 TI - Depression and quality of life for women in single-parent and nuclear families. AB - This is a cross-sectional study which objectives are 1) to determine the predictors for perceived quality of life and 2) to analyze the differences between women from single-parent families and bi-parent families, about their quality of life, depression and familiar income. We worked with a non probabilistic sample of 140 women from Monterrey, N.L, Mexico, 107 are from bi parent families and 33 from single parent families. Some of the results show that women from single-parent families have lower quality of life (Z = -2.224, p = .026), lower income (Z = -2.727, p = .006) and greater depression (Z = -6.143, p = .001) than women from bi-parental families. The perceived quality of life's predictors, using a multiple regression model (n = 140) were depression, income and number of children, those variables explaining 25.4% of variance. PMID- 19476231 TI - Efficacy of a social cognition training program for schizophrenic patients: a pilot study. AB - Psychosocial functioning impairment is recognized as a core feature of schizophrenia. Numerous studies have assessed the process that may underlie this impairment. In the last years, one of these processes that has been studied more is social cognition, which has been proposed as a mediator variable between neurocognition and functional outcome. Social cognition includes the subdomains of emotion recognition and social perception, and in recent years several authors have developed diverse training programs in these areas. The purpose of the present article is to assess the efficacy of the Social Cognition Training Program, a program that includes emotion recognition training and social perception training. The sample was made up of 14 outpatients with a diagnosis of schizophrenia according to CIE-10 criteria, randomly divided into two groups: experimental and control. All patients were assessed before and after the training program. Cognitive and psychopathological variables, social functioning, emotion recognition and social perception performance were assessed. Results suggest improvement in social perception and interpretation in the experimental group, in comparison with the control group, but not in emotion recognition. No significant correlations were obtained between social cognition training and other variables tested. PMID- 19476232 TI - Group psychotherapy of psychosomatic outpatients--analysis of the ten first sessions. AB - This work presents a description of a psychotherapeutic group of psychosomatic patients conducted in an out-patient setting. We show the gains of insight in the group's organization and inter-personal communication, as well as the relief of symptoms in seven patients attended by this psychoanalytically oriented group therapy. We discuss the extent and the limits of the group technique for such patients and we conclude with some proposals about the efficacy of this therapeutic approach. PMID- 19476233 TI - Love and emotional well-being in people with intellectual disabilities. AB - Love has been a recurrent topic throughout history, and especially, literature. Moreover, there is generalized agreement about its relevance for health emotional well-being, and quality of life. This study was carried out with a sample of 376 persons with ID. The goals of the work were to analyze a theoretical model of love in people with intellectual disabilities by means of the methodology of structural equations, and to analyze their perception of love and of amorous relations with regard to other aspects such as amorous satisfaction, perceived satisfaction, absence of family interference, self-determination, and emotional well-being. The results revealed that (a) the construct under study has three factors: Commitment, stability, and idealization, Passion and physiological excitement, and Intimacy and romanticism; (b) the perception of love in this collective is, in general, idealized and affected by the context; and (c) self determination and the lack of family interference are relevant variables to explain both love and emotional well-being. PMID- 19476234 TI - Practice of biopsychosocial medicine in Portugal: perspectives of professionals involved. AB - Although, recently, the biopsychosocial approach has been emphasized in the practice of family medicine, how psychologists and physicians interact in collaborative family health care practice is still emerging in Portugal. This article describes a qualitative study that focused on the understanding of psychologists and family physicians' perceptions of their role and the collaborative approach in health care. A questionnaire gathered information regarding collaboration, referral, training and the practice of biopsychosocial medicine. A content analysis on respondents' discourse was performed. Results show that both physicians and psychologists agree on the importance of the biopsychosocial model and interdisciplinary collaboration. However, they also mentioned several difficulties that have to do with the lack of psychologists working full time in health care centers, lack of communication and different expectancies regarding each other roles in health care delivery. Both physicians and psychologists acknowledge the lack of academic training and consider the need for multidisciplinary teams in their training and practice to improve collaboration and integrative care. Implications for future research and for the practice of biopsychosocial medicine are addressed. PMID- 19476235 TI - Assesment of social support dimensions in patients with eating disorders. AB - The aim of this study is to assess social support dimensions (providers, satisfaction and different support actions) in patients with eating disorders (ED), looking at diagnosis, socio-demographic and clinical characteristics, and self-concept. METHOD: A total of 98 female ED patients were recruited. The ages of participants ranged from 12 to 34 (Mean = 20.8-years-old, SD=5.61). Patients have a primary DSM-IV-R diagnosis of anorexia nervosa (61.2%), bulimia nervosa (27.6%) or an unspecified eating disorder (11.2%). Social support was assessed using the Escala de Apoyo Social Percibido (EASP). This scale measures social support providers, satisfaction and specific social support actions, which can be grouped into informational, emotional and practical support. Self-concept was assessed using the Cuestionario de Autoconcepto (AF-5). RESULTS: The two most frequent providers for these patients were mothers (86.7%) and partners (73.1%). Patients' satisfaction with social support was high and they reported that they received informational support more frequently than emotional and practical support. Family self-concept showed positive relationships with social support dimensions. CONCLUSION: These results show the importance of the family network in connection with these disorders and its relation to self-concept. PMID- 19476236 TI - Daily activity and life satisfaction in older people living in rural contexts. AB - This study is aimed at exploring daily and desired activity patterns in a sample of older people living in a rural context, as well as at examining the effect of some influential factors and their relationships with life satisfaction. Our sample was made of 216 retired people and was recruited from 12 villages from Catalonia and Valencia with populations of less than 1000 inhabitants. Data were gathered by means of an interview that included daily and ideal activities and life satisfaction (by applying the Life Satisfaction Index). Our results show that yesterday's pattern of activities is similar to an ideal pattern, although in the ideal day, our sample allocated more time to social activities and less time to passive activities such as watching TV or resting. In both cases, leisure activities and time spent working seem to play an important role in older people's life. Gender has a remarkable influence on patterns of activity, as women devoted more time to instrumental activities and less time to leisure. In general, differences between yesterday's and ideal activities were not related to life satisfaction. PMID- 19476237 TI - Young people's heroes in France and Spain. AB - Heroes play collectivist or individualist roles in imagination and self development. Representations of heroic figures in questionnaires given to French (n = 241) and Spanish (n = 227) samples of 10 and 15-year-olds were examined to assess the extent that heroes originated in digital media, and whether they were proximal or distal personalities. There is strong evidence that heroes in this sample were largely learned about in digital media (France 45%, Spain 50%): family and community heroes were a minority (France 11%, Spain 9%). Male heroes were more important to Spanish participants compared to their French peers. The acquisition sequence for hero type reported in the pre-television era, proximal (family and community) to distal (beyond the neighbourhood), is reversed in this study. Generally, 10-year-olds preferred heroes with collectivist qualities and 15-year-olds with individualised qualities. Findings are discussed in terms of the emergence of social capital. PMID- 19476238 TI - Attitude similarity and stereotypicality in leader evaluation. AB - Stereotypicality and attitudinal similarity are variables broadly studied in the research about leader's acceptance and evaluation. However, the interaction between these variables has not been deeply studied. An experimental research in which we analyze the influence of both variables and their interaction on leaders' evaluation is presented. A 3 x 3 (attitudinal similarity [none, moderate, high] x leaders' stereotypicality [none, moderately and very stereotypical]) design was used. Participants were 215 Psychology students. Results show that both variables influenced leaders' evaluation, although the influence of stereotypicality was stronger than that of attitude similarity. The significant interaction between both variables indicates that, when a very stereotypical leader is not at all similar or moderately similar to the perceiver, his or her evaluation diminishes. PMID- 19476239 TI - Organizational leadership: motives and behaviors of leaders in current organizations. AB - Organizational leadership is fundamental for the working and development of current organizations. It helps members of an organization to face transcendental challenges. One of the fundamental aspects of leaders is their personal characteristics and behaviour as perceived by their co-workers. Although research has established a relationship between these components, findings have failed to come up with any congruent evidence and further to this the organizations and contexts used are from several decades ago. This article, which forms part of the international GLOBE project, analyses the relationship between motives and behaviour as perceived by co-workers in organizations, using quantitative and qualitative methods and including technological innovations. Using samples from 40 corporate directors and 84 of their co-workers, from different companies, it confirms how the main motives of leaders (power, affiliation and achievement) are related to different behavioral patterns (power to authoritarian, non-dependent and non-social-skill behaviours; affiliation to relationship and dependent behaviors, and achievement to proactive behaviors). It discusses the results with relation to traditional research and suggests practical measures and proposals for future investigations in this area. PMID- 19476240 TI - Ombudsing in higher education: a contingent model for mediation in university dispute resolution processes. AB - University and academia are, due to its nature, its structure and its inside relationships, a perfect breeding ground for the conflicts, disputes, problems, and grievances. In these settings, mediation is one of the dispute resolution mechanisms most used by University Ombudsperson. However, the special characteristics of university contexts make it necessary to consider and evaluate elements that may have a bearing on the effectiveness of the process and outcomes of the mediation. In this paper a model of contingent intervention in mediation processes articulated in three dimensions is put forward: a) level of balance or symmetry of power between the parties involved; b) the foreseeable temporal perspective of the relationship between them; and c) level of formalization of the mediation process. Based on the interaction between the three dimensions, a series of proposals will be formulated in order to design different strategies of intervention for mediation processes in university settings. Practical implications of this contingent model and future research on this topic are discussed. PMID- 19476241 TI - Statistical inference involving binomial and negative binomial parameters. AB - Statistical inference about two binomial parameters implies that they are both estimated by binomial sampling. There are occasions in which one aims at testing the equality of two binomial parameters before and after the occurrence of the first success along a sequence of Bernoulli trials. In these cases, the binomial parameter before the first success is estimated by negative binomial sampling whereas that after the first success is estimated by binomial sampling, and both estimates are related. This paper derives statistical tools to test two hypotheses, namely, that both binomial parameters equal some specified value and that both parameters are equal though unknown. Simulation studies are used to show that in small samples both tests are accurate in keeping the nominal Type-I error rates, and also to determine sample size requirements to detect large, medium, and small effects with adequate power. Additional simulations also show that the tests are sufficiently robust to certain violations of their assumptions. PMID- 19476242 TI - On-line assessment of comprehension processes. AB - In this paper we describe a new version of a former paper-and-pencil standardized comprehension test called Test of Comprehension Processes (Vidal-Abarca, Gilabert, Martinez, & Selles, 2007). The new version has been adapted to a computer-based environment based on the moving window technique. It can be used to assess comprehension strategies of students from fifth to tenth grades (11- to 16-years-old). Comprehension strategies are registered on-line using reading times and visits to relevant sections of the text during the question-answering process. Data show that the computer-based version draws similar results to those provided by the paper-and-pencil version. In addition, we identify the particular strategies deployed during the question-answering process by high, medium and low comprehenders. PMID- 19476244 TI - Preliminary validation in Spanish of a scale designed to measure motivation in physical education classes: the Perceived Locus of Causality (PLOC) Scale. AB - The purpose of this paper was to validate the Spanish version of the Perceived Locus of Causality Scale (PLOC; Goudas, Biddle, & Fox, 1994). To achieve this, two studies with samples of 1535 and 400 physical education students, of ages 12 to 17 years, were carried out. The psychometric properties of the PLOC were examined through the following analyses: confirmatory factor analysis, factor invariance, correlation among factors, reliability (Cronbach's alpha), temporal stability (test-retest), and criterion validity. The results partially supported the five-factor structure. This structure was invariant across the two study samples. Correlations among the subscales indicated a simplex pattern, supporting construct validity of the scale. Alpha values over .70 (except for introjected regulation) and high temporal stability (intra-class correlation coefficient = .83 to .90) over a four-week period were obtained. The mastery-approach goal positively predicted self-determined motivation, whereas the performance avoidance goal predicted it negatively. Future studies should continue to analyze the psychometric properties of the PLOC, as the validation of an instrument should be an ongoing process. PMID- 19476243 TI - The Aggression Questionnaire for Spanish preadolescents and adolescents: AQ-PA. AB - We have already published the psychometric properties of our Spanish version of the Buss and Perry's Aggression Questionnaire adapted to young subjects (Personality and Individual Differences, 42, 1453-1465). The four-dimensional structure of the questionnaire was confirmed in each pre-adolescent and adolescent sample, although differences in the intercorrelations among factors between both groups of age were then observed. We publish now new evidences about its factorial validity in the whole group of pre-adolescent and adolescent children. We also report the positive correlations found between measurements obtained with this questionnaire (AQ-PA) and other aggression and anger scales (DIAS, STAXI and EXPAGG) and the Barratt Impulsiveness Scale (BIS-11), which provide more evidences about its convergent validity. The text of the Spanish version of this questionnaire adapted to pre-adolescent and adolescent subjects is also reported. PMID- 19476245 TI - Anxiety and coping strategies in sport contexts: a look at the psychometric properties of Portuguese instruments for their assessment. AB - The purpose of this study was to examine the psychometric properties of the Portuguese versions of the Sport Anxiety Scale and of the Brief COPE, as well as of the Cognitive Appraisal Scale in Sport Competition-Threat Perception, namely regarding their factor structure validity and internal consistency. Participants were 550 male and female athletes of several sports, aged 15- to 35-years-old (M=19.8; SD=4.5). Exploratory and Confirmatory Factor Analysis indicated that the instruments demonstrated good psychometric properties. In general, the measurement models provided a good fit to the empirical data and with the exception of some scales of the Brief COPE, the calculated Cronbach's a coefficient of reliability indicated adequate internal consistency for the three instruments. Overall, the results of the present study provided evidence for these instruments' validity and reliability, ultimately supporting their importance for research and psychological intervention in sport contexts. PMID- 19476247 TI - Psychometric properties of a brief version of the Escala de Satisfacao com o Suporte Social for children and adolescents. AB - The main objective of this study was to develop a brief version of the Escala de Satisfacao com o Suporte Social for children and adolescents (Ribeiro, 1999). A representative sample of 3195 children and adolescents was obtained from 5th and 7th graders throughout all five Portuguese regions. The results showed a good internal consistency for the social support satisfaction factor, alpha = 0.84; acceptable for the necessity for activities connected to social support factor, alpha = 0.69. By using ANOVA, gender, age and socioeconomic status related differences were identified. A confirmatory factorial analysis was done and an adjusted model was found by taking off item 5. The concurrent validity was inspected with measures related to social support, such as optimism, self-worth and perceptions of health related quality of life. With this analysis, we verified that women and younger participants (< 12 years) showed a higher social support satisfaction. Medium-high socioeconomic status participants showed a higher negative social support satisfaction. These results suggest the validity of the scale in assesing perceptions of social support. PMID- 19476246 TI - Construction and validation of the Brazilian Questionario de Respostas Socialmente Habilidosas Segundo Relato de Professores (QRSH-PR). AB - Behavioral problems in preschool children are one of the most frequent motives for seeking psychological care by parents and caregivers. Instruments are considered necessary, created from a Social Skills Training theoretical-practical perspective, which may systematically assist the identification of social skills and behavioral deficits, helping professionals in the prevention and/or reduction of behavioral problems. The purpose of this study was to test the psychometric validity and reliability of an instrument for evaluation of Socially Skilled Responses, from a teacher's perspective (QRSH-PR). For this purpose, 260 preschool children were evaluated, differentiated in subgroups without and without behavioral difficulties, based on the Child Behavior Scale (Escala de Comportamento Infantil/ECI-Professor). Studies were conducted for construct, discrimination, concurrent and predictive validity. The Cronbach Alpha was calculated to evaluate internal consistency. The obtained results pointed to positive indicators in reference to construct, discrimination, and predictive validity, and even for good internal consistency, indicating that the items consistently measure the construct of social skills, and differentiated children with and without behavioral problems. The questionnaire is considered to be gauged for evaluation of socially skilled responses from preschool children, and applicable in educational and clinical environments. PMID- 19476248 TI - Development of a questionnaire to evaluate coping strategies for skin problems. AB - The aim of this work was to develop an instrument (Coping Strategies for Skin Problems Questionnaire) suitable for identifying the coping strategies people use for general skin problems. We analyzed its psychometric properties when applied to a sample of 299 individuals. Factor analysis shows a 6-factor structure referring to the wish to change, problem-solving strategies, the search for information and asking for social support, the ability to distance oneself from the problem and to see the positive aspects of the situation. These factors explain 60.77% of the variance and show an internal consistency higher than 0.67. We analyse the validity of the questionnaire and identify different coping profiles depending on the degree of skin damage as assessed by the participants and their search for health services. According to the psychometric properties obtained, we conclude that our instrument is valid and reliable for use with people presenting skin problems. PMID- 19476249 TI - The "fashion-form" of modern society and its relationship to psychology. AB - In this work, we present a new way of understanding psychology, which emerges as a result of relating it to the three principles of the theory of fashion of Gilles Lipovetsky: "the principle of the ephemeral," "the principle of the marginal differentiation of individuals," and "the principle of seduction." We relate the first principle to the plurality of the diverse and changing "schools and systems" that have existed throughout the history of psychology. We apply the second to the figure of the psychologist, considered individually, revealing his or her leading role in the generation of the changing plurality of the systems. By means of the third principle, we point up that the diverse psychologies are forms of seduction. We conclude by stating that psychology has the form of fashion and we analyze how this form can help us to better understand it. PMID- 19476250 TI - Clustering of metabolic factors among the patients with essential hypertension. AB - The prevalence of metabolic syndrome was determined in clinic-based 1,517 hypertensive patients. All traits were present in 1.1% men and 12.8% women. Combination of different three traits were present as follows: hypertension with high triglyceride and low HDL (men 29.4% vs. women 51.8%), hypertensio with high blood glucose and low HDL (men 13.5% vs. women 29.8%), hypertension with high glucose and high triglyceride (men 18.1% vs. women 18.1%), hypertension with high blood glucose and large waist (men 2.7% vs. women 25.7%), hypertension with high triglyceride and large waist (men 3.4% vs. women 39.3%) and hypertension with low HDL and large waist (men 2.5% vs. women 70.6%). The study shows that the metabolic syndrome is highly prevalent among hypertensive patients especially women. PMID- 19476251 TI - Quality gap of educational services at Zahedan University of Medical Sciences, Iran. AB - This study aims to compare quality gap of educational services at Zahedan University of Medical Sciences from students and faculties viewpoints. In a cross sectional study, survey questionnaire was completed by two distinct groups of respondents- 230 faculty members and 384 students. Mass majority of the both groups declared there was negative gap in each of the five dimensions. Mean quality gaps from viewpoint of both groups were negative. The largest mean quality gap from students and faculty members viewpoint was in the responsiveness and tangibility dimensions respectively. The largest and smallest differences between students and faculties viewpoint were in the responsiveness and tangibility dimensions. PMID- 19476252 TI - Socio-economic determinants of low birth weight in Bangladesh: a multivariate approach. AB - Though the health situation of Bangladesh has improved substantially over the years, the low birth weight (LBW) rate is still pretty high. The principal focus of this study was to ascertain the significant determinants for LBW. One hundred and eight LBW babies were compared with 357 normal birth weight babies. Out of 20 possible risk variables analyzed, 9 were found significant when studied separately. Mother's age, education, occupation, yearly income, gravid status, gestational age at first visit, number of antenatal care visit attended, quality of antenatal care received and pre-delivery body mass index had significantly associated with the incidence of LBW. Using the stepwise logistic regression, mother's age (p < 0.001), education (p < 0.02), number of antenatal care visit attended (p < 0.001, OR = 29.386) and yearly income (p < 0.001, OR = 3.379) created the best model, which predicted 86.1% and 94.4% of the LBW babies and normal birth weight babies respectively. Maternal age, educational level and economic status play an important role in the incidence of low birth weight. PMID- 19476253 TI - Malaria in southeast Bangladesh: a descriptive study. AB - Malaria in Asia is thought to be grossly under-reported and this is evident from previously published statistics from Bangladesh. Malaria screening data from four Upazillas was analysed alongside census data to assess the trends in malaria incidence over time and distribution of malaria by age and gender. Malaria incidence in this area has decreased by around two thirds since 2003, although control measures were not significantly increased until 2005. Malaria occurred in people of all ages with the highest incidence being in young adults. This is consistent with higher occupational exposure in this group. The probability of being screened for malaria decreased with age suggesting significant numbers of adults with malaria may be being missed. PMID- 19476254 TI - Acute and long-term neurological complications in children with acute lymphoblastic leukemia. AB - The pattern of acute and long-term neurological complications in 133 children with acute lymphoblastic leukemia (ALL) treated with two treatment protocol was reviewed. Twenty patients developed neurological complications. Nine out of 20 patients received MRC UK ALL X and the remaining 11 received MRC UK ALL XI protocol. There was no difference of neurological complications between MRC UKALL X and UK ALL XI protocol groups. The numbers of patients who developed neurological complications during induction of remission period were 11 of 133 patients (8.2%). 122 patients were observed during the maintenance period of treatment (from 6 months to 36 months). Six out of 122 patients developed neurological complications during this period. 88 patients were followed for a period of up to 6 months after the cessation of chemotherapy, i.e., in the late period. Neurological complications were found in 3 during this period. Neurological complications rate was 4 times higher in the relapsed group than in the no relapsed group (p < 0.05). Systemic chemotherapy (including vincristine, high-dose methotrexate) and intrathecal chemotherapy seem to be the most common predisposing factors. PMID- 19476255 TI - Immune thrombocytopenic purpura among the children attending at two teaching hospitals. AB - The presenting features, diagnostic evaluation, seasonal variation and management performed in 110 children with immune thrombocytopenic purpura (ITP) attending at two tertiary level hospitals were evaluated. A peak incidence of children with ITP was observed during the month of June, July and the first step was found in May and lowest in the month of October to December. Mean initial platelet count was 65.5 x 10(9)/L. 35 patients with ITP did not require any treatment who were kept under observation and the rest 75 children who were admitted to hospital given platelet count enhancing treatment- intravenous immunoglobulin in 9, corticosteroids in 60 or both in 6 children with ITP. Intracranial hemorrhages were noticed in two children with ITP. So, this study suggests that ITP had special predilection during summer season and the least in winter along with variable approaches to management of these children. PMID- 19476257 TI - Protective effect of tomato against adrenaline-induced myocardial infarction in rats. AB - Lycopene, a carotenoid rich in tomato fruit (ripe), is an effective antioxidant and free radical scavenger. In this study n-hexane extract of tomato was evaluated for its protective action against oxidative stress in experimental myocardial infarction induced by administration of adrenaline in rats. Adrenaline produced significant elevation of malondialdehyde content of heart, an indicator of lipid peroxidation, with a significant rise in serum aspartate aminotransferase (AST) level and different grades of necrotic changes in myocardium. Rats were treated with two doses of n-hexane extract of tomato, intragastrically daily for one month prior to administration of adrenaline on the 31st and 32nd day. Pretreatment of tomato extract (1 mg/kg, 2 mg/kg) and vitamin E (50 mg/kg) significantly reduced the malondialdehyde concentration in heart and significantly lowered the serum AST level in adrenaline treated rats. Myocardial necrosis was significantly prevented by pretreatment. These results suggest that n-hexane extract of tomato possesses antioxidative property that may protect heart against catecholamine induced myocardial infarction. PMID- 19476256 TI - Major post-operative complications of thyroid surgery: preventable or not? AB - Factors responsible for major complications following thyroid surgery in 598 patients were studied. Patients with non toxic multinodular goiter involving both lobes of thyroid constituted the maximum bulk subjected to thyroidectomy. The most frequent procedure was bilateral subtotal thyroidectomy. Reactionary hemorrhage occurred in 6 patients, all following bilateral procedures and among them 5 patients developed tension hematoma with respiratory obstruction despite the presence of a drain. Temporary vocal cord palsy was observed in 7 patients whereas one patient subjected to total thyroidectomy with neck dissection for papillary carcinoma of thyroid developed permanent right vocal cord palsy. Temporary parathyroid insufficiency was seen in 51 patients and one patient developed permanent hypoparathyroidism. Incidence of parathyroid insufficiency was higher in bilateral procedures as compared to unilateral ones. There was no operation related death in this series, but complications like hemorrhage, vocal cord palsy and parathyroid insufficiency following thyroid surgery are still a deep concern. PMID- 19476258 TI - Post-operative analgesic in children. PMID- 19476259 TI - Glyceryl trinitrate: the management of chronic anal fissure in patients who are unfit for surgery. PMID- 19476261 TI - Bevacizumab in the treatment of metastatic breast cancer. AB - Increased levels of vascular endothelial growth factor (VEGF) have been associated with a poor prognosis for patients with breast cancer. In addition to its prognostic role, VEGF is also a validated target in the treatment of this disease. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors, including breast cancer. Its use in combination with either paclitaxel or docetaxel has prolonged progression-free survival and increased response rates in the first-line treatment of patients with metastatic, HER2-negative breast cancer. In this paper, the clinical trials establishing bevacizumab use for the treatment of breast cancer are reviewed. PMID- 19476260 TI - Efficacy of nebulized ipratropium bromide versus salbutamol in infants with acute bronchiolities. PMID- 19476262 TI - Bevacizumab in breast cancer: the best is yet to come? PMID- 19476263 TI - Optimizing outcomes with bevacizumab by better targeting patients and tumors. PMID- 19476264 TI - The role of adjuvant radiation in endometrial cancer. AB - Endometrial cancer treatment ideally begins with a staging procedure including abdominopelvic washing, total abdominal hysterectomy, bilateral salpingo oophorectomy, and lymph node evaluation. Recommendations for postoperative adjuvant radiotherapy are determined by recurrence risk. Patients who have undergone staging and have early stage I disease and an absence of high-risk features for recurrence generally are treated with surgery alone. Intermediate risk patients--those with high-risk stage I disease and some stage II patients- may benefit from adjuvant radiation therapy. Several randomized trials show that radiation therapy improves locoregional control among intermediate-risk patients. The optimal type of radiation therapy, whether vaginal brachytherapy or whole pelvic radiation therapy, remains undetermined, though treatment decision can be guided by risk factors not encompassed by the current staging system. Patients with high-risk stage II disease and stage III disease generally receive external beam radiotherapy, often in combination with chemotherapy. Chemotherapy alone in advanced-stage patients is a consideration, given the results of the Gynecologic Oncology Group (GOG)-122 trial. PMID- 19476265 TI - Resolving the confusion surrounding adjuvant radiation in endometrial cancer. PMID- 19476266 TI - Studies of adjuvant treatment for endometrial cancer. PMID- 19476267 TI - Health literacy, communication, and treatment decision-making in older cancer patients. AB - Inadequate health literacy and physician-patient communication are associated with poor health outcomes and appear to limit quality of medical decision-making. This review presents and consolidates data concerning health literacy, physician patient communication, and their impact on medical treatment decisions in elderly cancer patients. This population faces increasingly complex management options, cognitive and sensory deficits, and intergenerational barriers. As a result of these and other factors, older cancer patients have among the lowest health literacy and numeracy rates and often suffer from suboptimal physician-patient communication. These deficiencies impair elderly cancer patients' ability to understand, recall, and act upon information concerning treatment risk and benefit. This situation also makes it difficult for patients to have self confidence in communicating with their provider and sharing in the decision making. Moreover, since older cancer patients usually bring a companion to medical appointments, the positive and negative role of a companion in the context of communication and decision-making needs to be considered. Future research should center on developing ways to identify and overcome health communication barriers to improve geriatric cancer care. PMID- 19476268 TI - Health literacy: improving patient understanding. PMID- 19476269 TI - Current status and future potential of advanced technologies in radiation oncology. Part 2. State of the science by anatomic site. AB - In December 2006, the Radiation Research Program of the Division of Cancer Treatment and Diagnosis of the National Cancer Institute hosted a workshop intended to address current issues related to advanced radiation therapy technologies, with an eye toward (1) defining the specific toxicities that have limited the success of "conventional" radiation therapy, (2) examining the evidence from phase III studies for the improvements attributed to the advanced technologies in the treatment of several cancers commonly treated with radiation therapy, and (3) determining the opportunities and priorities for further technologic development and clinical trials. The new technologies offer substantial theoretical advantage in radiation dose distributions that, if realized in clinical practice, may help many cancer patients live longer and/or better. The precision of the advanced technologies may allow us to reduce the volume of normal tissue irradiated in the vicinity of the clinical target volume. Part 1 of this two-part article, which appeared in the March issue of ONCOLOGY, provided a general overview of the workshop discussion, focusing on the challenges posed by the new technologies and resources available or in development for meeting those challenges. This month, part 2 will outline the state of the science for each disease site. PMID- 19476271 TI - Evaluating advanced technologies in radiation oncology: when and how should randomized trials be done? PMID- 19476270 TI - Clinical trials and radiation oncology technologies. PMID- 19476272 TI - Complementary therapies, herbs, and other OTC agents. PMID- 19476273 TI - Emerging therapies for multiple myeloma. AB - In the past decade, the therapeutic landscape for myeloma has changed dramatically with the advent of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib). These agents alone have activity against myeloma with even better responses when combined with additional agents such as steroids and chemotherapy. Initially introduced for relapsed/refractory disease, these agents are being increasingly tested in the upfront setting with improvement in response rates and prolongation of responses. We review the key findings from recently completed and ongoing studies that evaluate the effect of the novel therapies, both in newly diagnosed myeloma and in relapsed disease. The use of these agents in specific settings is also discussed. PMID- 19476274 TI - Maximizing the clinical benefit of novel therapies in multiple myeloma. PMID- 19476275 TI - Treatment of multiple myeloma: whence truth over belief? PMID- 19476277 TI - Use of high-resolution CT imaging data in lung cancer drug development: measuring progress. PMID- 19476276 TI - Surprised by stage III: unexpected N2 lymph node involvement found during surgery for early-stage NSCLC. AB - Dr. Camidge: To summarize, this patient is a relatively young, otherwise healthy female who is status post lobectomy. She has been diagnosed with stage IIIA NSCLC that is EGFR-positive by IHC and FISH, but EGFR and KRAS wild type. Optimal MLNS or MLND is ideally performed in the pre- and/or perioperative setting, but this did not happen in this case. While more extensive examination of the mediastinum after the primary operation could be undertaken--removing some of the unknowns about this patient's true stage and prognosis--the relative risks and benefits of such an additional procedure in the setting of PET-negative microscopic level 7 and 9 disease probably do not justify such an approach. Assuming the absence of additional information, the recommendation of the University of Colorado Clinical Thoracic Oncology program is to commence a course of four cycles of adjuvant cisplatin-based chemotherapy. The pros and cons of postoperative radiotherapy will be discussed with the patient. If she wishes to proceed with PORT, this will commence following the adjuvant chemotherapy. Due to the inadequate lymph node sampling, she would not be eligible for adjuvant therapy as part of the ECOG 1505 trial of cisplatin chemotherapy with or without bevacizumab, but if she declines PORT, she may be eligible for the RADIANT trial of erlotinib vs placebo following her adjuvant cisplatin-based therapy. PMID- 19476278 TI - Efficacy of select disinfectants at inactivating Ranavirus. AB - Ranavirus can cause disease in reptiles and amphibians. Because survival time outside of a host remains uncertain, equipment must be disinfected to prevent transmission of ranaviruses. However, disinfectant efficacy against amphibian ranaviruses has not been investigated for chlorhexidine (Nolvasan), sodium hypochlorite (bleach), or potassium compounds. Our goal was to determine the efficacy of Nolvasan (0.25, 0.75 and 2.0%), bleach (0.2, 1.0, 3.0 and 5.0%), and Virkon S (1.0%) at inactivating Ranavirus at 1 and 5 min contact durations. Potassium permanganate (KMnO4) (2.0 and 5.0 ppm) was also tested with a 60 min contact time. Nolvasan at 0.75 and 2.0% and bleach at 3.0 and 5.0% concentration were effective for both contact durations. Virkon S was effective for both durations, but KMnO4 was not effective at either concentration. Concentrations of Nolvasan, bleach and Virkon S that are at least 0.75, 3.0 and 1.0%, respectively, are effective at inactivating Ranavirus after 1 min exposure time. PMID- 19476279 TI - Pathology, isolation and molecular characterisation of a ranavirus from the common midwife toad Alytes obstetricans on the Iberian Peninsula. AB - We describe the pathology, isolation and characterisation of a virus responsible for an outbreak of a systemic haemorrhagic disease causing high mortality in tadpoles of the common midwife toad Alytes obstetricans in the 'Picos de Europa' National Park in northern Spain. The virus, provisionally designated as the common midwife toad virus (CMTV), was isolated from homogenates of visceral tissue from diseased toad tadpoles following inoculation on epithelioma papulosum cyprini (EPC) cells. Molecular characterisation of the virus, including sequence analysis of the DNA polymerase and major capsid protein genes, showed that the isolated virus was a ranavirus with marked sequence identity to other members of the genus Ranavirus. A rabbit antiserum raised against purified virions was prepared and used to definitively demonstrate systemic distribution of the virus in diseased tadpoles, indicating that the isolated virus was the primary pathogen. PMID- 19476280 TI - Epidemiologic investigation of the re-emergence of infectious salmon anemia virus in Chile. AB - Reports from surveillance activities were analyzed to determine the epidemiology of the re-emergence of infectious salmon anemia virus (ISAV) in Atlantic salmon farms in Chile. The epidemic and spatial and spatiotemporal patterns were described, taking into account commercial compartmentalization of the farms. During the 64 wk study period, 76 ISAV-infected salmon farms, representing 17 companies, were reported in 65% of the management geographic zones of the 10th region in southern Chile. Approximately 20% of the farms at risk became infected, with the incidence rate increasing slightly over time. Results from epidemic analyses and observed spatial and spatiotemporal patterns suggested an initial dispersal and subsequent clustering of cases around the index case (IC) in a propagated epidemic mode. Results suggested that delayed depopulation may have been a key factor in the spread and persistence of ISAV. Clustering of cases supported the assumption that passive transmission in seawater from ISAV-infected farms (proximity) is a critical factor in controlling disease. The re-emergence of ISAV in Chile has resulted in one of the largest ISAV epidemics reported in the world and this study generates new hypotheses and provides useful information for spatial disease control planning in salmon farming areas. PMID- 19476281 TI - Characterization of proteins secreted from a type III secretion system of Edwardsiella tarda and their roles in macrophage infection. AB - The Type III secretion system is essential for intracellular replication of Edwardsiella tarda in phagocytes of fish and mammals. We identified the secreted proteins of the Type III secretion system by comparing the wild-type strain and the Type III mutant mET1229. The wild-type strain secreted 55, 25, and 22 kDa proteins into the culture supernatant, whereas the Type III mutant did not. These proteins were identified as EseB, EseC, and EseD and are similar in sequence to Salmonella SseB, SseC, and SseD that function as a translocon. The EseB, EseC, and EseD knockout mutants did not replicate in murine macrophages, suggesting that these proteins are essential for intracellular replication of E. tarda. Highest secretion of EseBCD proteins was observed when bacterial cells were cultured in neutral and alkaline pHs but not in acidic pH. When the pH of the phagosomes was examined using an acidotropic probe, the phagosomes containing the wild-type strain showed neutral pH, whereas those containing the Type III mutant exhibited acidic pH. These results suggest that the Type III-dependent interference with formation of the acidic environment in phagosomes is essential for intracellular replication of bacteria in murine macrophages. PMID- 19476282 TI - In vivo exposure of susceptible and non-susceptible fish species to Myxobolus cerebralis actinospores reveals non-specific invasion behaviour. AB - Due to controversial previous results, it has been unclear whether Myxobolus cerebralis (Myxosporea, Myxozoa) is able to specifically choose a salmonid host by selective attachment and penetration. Using a novel in vivo tracking assay that employs fluorescence staining of actinospore sporoplasms, we demonstrate a lack of host specificity of M. cerebralis actinospores during their initial invasion reactions. Fish were experimentally exposed to stained actinospores that could be detected as emitted sporoplasms in and on the fish integument of skin, gills and fins. There were no significant differences in the number of actively emerging sporoplasms found on epithelial surfaces of a susceptible and resistant strain of rainbow trout and common carp after experimental exposure. Numbers of parasite attachment rates to carp and trout gill tissue were also assessed using quantitative real-time PCR (qPCR). This method demonstrated that actinospore reactivity rate was not affected by the staining procedure. An even higher number of parasite stages was detected in carp than in trout gills. Subsequently, the ability of carp to lower the infection severity of susceptible rainbow trout by trapping the parasites under natural conditions was also investigated. Myxospore load was significantly reduced in hosts infected with actinospore samples that were preincubated with live carp. These results indicate the possibility of biological disturbance to the life cycle of the parasite in the wild by interceptor fish species as one measure to prevent whirling disease. PMID- 19476283 TI - Infection threshold to estimate Lepeophtheirus salmonis-associated mortality among juvenile pink salmon. AB - A threshold of lethal infection was estimated from previous controlled laboratory exposures to be 7.5 Lepeophtheirus salmonis g(-1) for pink salmon Oncorhynchus gorbuscha averaging < 0.7 g. This threshold was used to assess the risk of mortality caused by L. salmonis among pink salmon of the same size class in the Broughton Archipelago, Canada from 2005 to 2008. Virtually all (> or = 98.9%) pink salmon collected in late March belonged to this size class, and this proportion declined to < or = 1% by early July. The proportion of these small pink salmon with infections equal to or exceeding the threshold declined from 4.5 in 2005 to 0% in 2008, coincident with an overall decline in parasite prevalence and intensity during this period. In 2005 and 2006, this proportion was greatest in March (7.8 and 1.1%, respectively) whereas in 2007, the proportion exceeding the threshold was greatest in May (2.9%). In 2008, no infections exceeded the threshold. Parasite development coincided with fish migration through the study area. The declining risk between 2005 and 2008 was possibly related to changes in ocean conditions such as temperature, to changing treatment practices for this parasite on salmon farms, or to changes in the abundance or distribution of non farmed hosts. The concept of a threshold of L. salmonis infection density may be used to assist in the management and conservation of juvenile pink salmon in the Broughton Archipelago region. PMID- 19476284 TI - Evaluation of fast green FCF dye for non-lethal detection of integumental injuries in juvenile Chinook salmon Oncorhynchus tshawytscha. AB - A rapid staining procedure for detection of recent skin and fin injuries was tested in juvenile Chinook salmon Oncorhynchus tshawytscha. Immersion of anesthetized fish for 1 min in aerated aqueous solutions of the synthetic food dye fast green FCF (Food Green 3) at concentrations of 0.1 to 0.5% produced consistent and visible staining of integumental injuries. A 0.1% fast green concentration was satisfactory for visual evaluation of injuries, whereas a 0.5% concentration was preferable for digital photography. A rinsing procedure comprised of two 30 s rinses in fresh water was most effective for removal of excess stain after exposure of fish. Survival studies in fresh water and seawater and histopathological analyses indicated that short exposures to aqueous solutions of fast green were non-toxic to juvenile Chinook salmon. In comparisons of the gross and microscopic appearance of fish exposed to fast green at various times after injury, the dye was observed only in areas of the body where epidermal disruption was present as determined by scanning electron microscopy. No dye was observed in areas where epidermal integrity had been restored. Further comparisons showed that fast green exposure produced more consistent and intense staining of skin injury sites than a previously published procedure using trypan blue. Because of its relatively low cost, ease of use and the rapid and specific staining of integumental injuries, fast green may find widespread application in fish health and surface injury evaluations. PMID- 19476285 TI - Lobomycosis-like disease and other skin conditions in Indo-Pacific bottlenose dolphins Tursiops aduncus from the Indian Ocean. AB - Lobomycosis is a chronic mycotic disease of the skin and subdermal tissues caused by the yeast-like organism Lacazia loboi, which affects humans and Delphinidae. Cases of lobomycosis and lobomycosis-like disease (LLD), a disease very similar to lobomycosis but for which a histological diagnostic is missing, have been reported in small cetaceans from the Americas and Europe. Here we report on LLD in Indo-Pacific bottlenose dolphins Tursiops aduncus from the tropical lagoon of Mayotte, between Mozambique and Madagascar. From July 2004 to June 2008, boat surveys were conducted in Mayotte waters. At least 71 adult dolphins were photo identified. Six (5 males, 1 female) had multiple raised, greyish nodules on the dorsal fin, head, flanks, belly, back and tailstock that suggested LLD. The lesions were extensive in some cases. The calf of the positive female was also affected. LLD has been present in this community since at least 1999. As sampling was not possible, the aetiology of the disease could not be explored. The emergence of LLD in Mayotte may be related to degradation of the coastal environment associated with rapid urbanization, expanding agriculture and increased release of untreated freshwater runoffs. Other skin lesions included scars, healing wounds, whitish lesions and lumps. PMID- 19476286 TI - Chytridiomycosis in frogs from Uruguay. AB - Amphibian chytridiomycosis caused by Batrachochytrium dendrobatidis is reported in Uruguayan native amphibians for the first time. Histological evidence of infection was observed in tadpoles of Hypsiboas pulchellus, Odontophrynus maisuma, Physalaemus henselii, and Scinax squalirostris. The effects of chytridiomycosis on these species are still unknown. However, the disease is of potential concern for the conservation of the apparently declining species P. henselii and also for O. maisuma, given its restricted distribution in habitats which are being increasingly disturbed. PMID- 19476287 TI - Non-invasive sampling methods for the detection of Batrachochytrium dendrobatidis in archived amphibians. AB - Chytridiomycosis, an emerging infectious disease of amphibians caused by the chytrid fungus Batrachochytrium dendrobatidis (Bd), is associated with amphibian population declines worldwide. Investigation of the origin and spread of the pathogen requires examination of archived museum specimens of amphibians. Examination for Bd infection is usually done using histological techniques, which are often too destructive for valuable museum material. Three alternative methods for Bd detection (skin swabbing, brushing and scraping) were evaluated for ability to yield Bd DNA and destructiveness to specimens. Archived amphibians known to be Bd positive and which had been preserved in either formalin or ethanol for many years were used. Samples were analysed using a Bd-specific quantitative real-time Taqman PCR (qPCR) assay. There was no difference in the ability of each of the techniques to detect Bd infection, with the pathogen being detected in 75 to 81% of the 16 ethanol-fixed frogs examined. Visible evidence of sampling was left by scraping, but not by swabbing or brushing. The brush-qPCR technique detected higher counts of genomic equivalents than the other 2 sampling methods, although differences were not statistically significant. The qPCR assay did not detect Bd from any of the 6 formalin-fixed frogs examined, regardless of the sampling method. Nondestructive sampling techniques enable qPCR analysis of ethanol-preserved museum specimens for Bd. Recently, the incorporation of DNA cleanup steps allowed the detection of Bd in destructively sampled tissues from formalin preserved specimens. Further studies using nondestructive sampling incorporating DNA cleanup steps for the detection of Bd in formalin preserved specimens are warranted. PMID- 19476288 TI - Application of YHV-protease dsRNA for protection and therapeutic treatment against yellow head virus infection in Litopenaeus vannamei. AB - While farming of the Pacific white shrimp Litopenaeus vannamei is well established in North and South America, the industry has more recently been introduced to Asia, and the Pacific white shrimp is now the most commonly farmed species in Thailand. However, outbreaks of yellow head virus (YHV) disease in the Pacific white shrimp have caused severe economic losses and currently there is no effective prevention or treatment of YHV infections. The YHV-protease double stranded RNA (YHV-Pro dsRNA) can act as both a prophylactic agent and as a treatment to inhibit YHV replication in infected black tiger shrimp Penaeus monodon. The utility of this methodology to other shrimp species has not, however, been established. The purpose of this study was to determine whether YHV Pro dsRNA can be applied to the Pacific white shrimp. To assess prophylactic efficiency, YHV-Pro dsRNA was injected into juvenile shrimp 24 h prior to challenge with YHV. Subsequent YHV replication was inhibited by YHV-Pro dsRNA as compared with injection of an unrelated dsRNA. For therapeutic treatment of YHV infected shrimp, shrimp were challenged with YHV before dsRNA injection. Injection of YHV-Pro dsRNA up to 6 h post-infection resulted in the almost complete elimination of YHV replication. These results suggest that YHV-Pro dsRNA can also be broadly applied as a prophylactic agent to inhibit YHV replication and therapeutic treatment of YHV-infected Pacific white shrimp. PMID- 19476289 TI - Helicobacter pylori in water sources: a global environmental health concern. AB - Helicobacter pylori are Gram-negative micro-aerophilic motile curve rods that inhabit the gastric mucosa of the human stomach. The bacterium chronically infects billions of people worldwide and is one of the most genetically diverse of bacterial species. More than half of the world population in both developed and developing countries are infected with this organism. Infection usually occurs without overt clinical symptoms, particularly in poor communities. If untreated, the infection can last for decades without causing symptoms. In some communities, however, infection with the organism causes peptic and duodenal ulcers, gastritis, duodenitis, and gastric cancers. How H. pylori initially enters the stomach is not known, but contaminated food particles and water are suspected, with the former physically shielding it from stomach acid. Similarly, the route of transmission of this pathogen is unknown. Several reports have suggested the possibility of waterborne transmission as the organism can survive for a few days in fresh cold water, salt water, distilled water, and tap water. Knowledge of the epidemiology and mode of transmission of H. pylori is important to prevent its spread and may be useful in identifying high risk populations. PMID- 19476291 TI - The urban elderly in the United States: health status and the environment. AB - A large number of elderly persons live in United States metropolitan areas and center cities. Although the urban environment can be supportive of health, the urban elderly face issues of decrease in organ function and reserves; impaired chemical clearance and detoxification; vulnerability to medication-environment adverse interactions (heat/psychotropic drugs); legacy of past occupational and environmental cumulative exposures to persistent agents; overall poorer health status; decreased ability to respond to disasters, emergencies, and extreme conditions; decreased ability to access good and services outside their homes; and increased sensitivity to environmental conditions. Planning for these challenges can create a supportive environment and improve the health of the urban elderly. PMID- 19476292 TI - An apple a day may hold colorectal cancer at bay: recent evidence from a case control study. AB - Environmental factors play an important role in the etiology of colorectal cancer, the second-most common malignancy in both genders in developed countries. Evidence has shown that potential cancer-inducing oxidative damage might be prevented or restricted largely by the presence of dietary antioxidants of plant origin, such as fruits or vegetables. The protective antioxidant effect of fruits and vegetables has been attributed to flavonoids, a major class of phytochemicals naturally occurring in fruits, vegetables, and various foods of plant origin. Yet, epidemiologic cohort studies relating flavonoid intake to risk of colorectal cancer have been sparse and inconclusive. Apples are a rich source of flavonoids and have the second highest level of antioxidant power among all fruits, with peels having a stronger antioxidant activity than apple flesh. A recent reanalysis of several case-control studies in Italy demonstrated a consistent inverse association between apple consumption and the risk of various cancers, and among them ofcolorectal cancer. Here we assessed the potential protective impact of apples on risk of colorectal cancer in the course of a recently performed hospital-based case-control study in a country with dietary habits very different from those of Mediterranean region. The results showed that highest risk of colorectal cancer was among older persons and those who were residents of villages or small towns. The risk of colorectal cancer was inversely correlated with daily number of apple servings, but the most significant reductions of OR estimates were observed for an intake one or more apple servings daily (OR = 0.37, 95% CI: 0.15-0.91). No other fruit was significantly associated with altering the risk of colorectal cancer. PMID- 19476293 TI - Back to Rome (criteria). PMID- 19476294 TI - Functional abdominal pain in children: new understanding, diagnostic criteria, and treatment approaches. AB - From the array of articles, one can readily see the clinical and scientific progress made in symptom-based diagnosis and management of functional abdominal pain disorders over the past 5 years. We have provided a series of useful tools to approach these patients. We have provided the symptom-based diagnostic criteria plus the red flags to help you avoid missing an organic diagnosis. We have placed these disorders squarely within the complex biopsychosocial framework by identifying early life stress and many environmental factors that are key factors in the development of pain. We have identified the role of psychological comorbidities of anxiety and depression and the need to address them directly in order to rehabilitate a disabled child. Finally, pharmacologic, psychological, dietary, and complementary approaches are reviewed and recommended as empiric therapy in functional abdominal pain, functional dyspepsia, and irritable bowel syndrome. Use these new tools well. PMID- 19476295 TI - A 4-month-old boy with cardiopulmonary arrest. PMID- 19476296 TI - A 6-week-old boy with apnea and abdominal distention. Late-presenting congenital diaphragmatic hernia. AB - Late-presenting CDH can present with a variety of symptoms. Radiographic evaluation may initially be normal or interpreted. It is important for clinicians to consider late-presenting CDH in the differential diagnosis of patients with respiratory and gastrointestinal symptoms. PMID- 19476297 TI - Functional abdominal pain: all roads lead to Rome (criteria). PMID- 19476298 TI - Navigating recurrent abdominal pain through clinical clues, red flags, and initial testing. AB - Recurrent abdominal pain is a common chronic complaint that presents to your office. The constant challenge is one of detecting those with organic disease from the majority who have a functional pain disorder including functional dyspepsia, irritable bowel syndrome, functional abdominal pain, and abdominal migraine. Beginning with a detailed history and physical exam, you can: 1) apply the symptom-based Rome III criteria to positively identify a functional disorder, and 2) filter these findings through the diagnostic clues and red flags that point toward specific organic disease and/or further testing. Once a functional diagnosis has been made or an organic disease is suspected, you can initiate a self-limited empiric therapeutic trial. With this diagnostic approach, you should feel confident navigating through the initial evaluation, management, and consultation referral for a child or adolescent with recurrent abdominal pain. PMID- 19476290 TI - Neurotoxic effects and biomarkers of lead exposure: a review. AB - Lead, a systemic toxicant affecting virtually every organ system, primarily affects the central nervous system, particularly the developing brain. Consequently, children are at a greater risk than adults of suffering from the neurotoxic effects of lead. To date, no safe lead-exposure threshold has been identified. The ability of lead to pass through the blood-brain barrier is due in large part to its ability to substitute for calcium ions. Within the brain, lead induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurologic disorders. At the molecular level, lead interferes with the regulatory action of calcium on cell functions and disrupts many intracellular biological activities. Experimental studies have also shown that lead exposure may have genotoxic effects, especially in the brain, bone marrow, liver, and lung cells. Knowledge of the neurotoxicology of lead has advanced in recent decades due to new information on its toxic mechanisms and cellular specificity. This paper presents an overview, updated to January 2009, of the neurotoxic effects of lead with regard to children, adults, and experimental animals at both cellular and molecular levels, and discusses the biomarkers of lead exposure that are useful for risk assessment in the field of environmental health. PMID- 19476299 TI - Functional abdominal separation anxiety: helping the child return to school. PMID- 19476301 TI - Early life stress and pain: an important link to functional bowel disorders. PMID- 19476300 TI - Treatment approaches to irritable bowel syndrome. PMID- 19476302 TI - Psychiatric comorbidity and functional abdominal pain. PMID- 19476304 TI - [Prioritization in health care--a discussion takes a journey]. PMID- 19476303 TI - Treatment options for functional gastrointestinal disorders: from empiric to complementary approaches. PMID- 19476305 TI - [Relationship between prioritisation and rationing--two models]. AB - The starting point of the present paper is the different uses of the terms prioritisation and rationing in the debate about resource allocation in health care. Two models of the relationship between prioritisation and rationing are developed. They are intended to contribute to a deeper understanding of the basic concepts. The first model of explicit priority setting assumes deliberate prioritisation which may form the basis of explicit rationing, but also of rationalisation and quality improvements. The second model, representing the rationing perspective, conceives rationing as a societal phenomenon whose implicit prioritisation criteria have to be deduced by means of interpretation. The two models can be distinguished from each other both theoretically and by their application in practice. Some advantages and disadvantages of the models are discussed. PMID- 19476306 TI - [Prioritisation in health care: learning from international experiences]. AB - In contrast to Germany, several other countries started to develop methods for setting priorities in health care more than 20 years ago. This paper provides an overview of the experiences in Norway, Sweden, the Netherlands, the United Kingdom and the US state of Oregon. Acknowledging the fact that - due to the increasing discrepancy between medical demand and publicly available financial resources--it is inevitable to set limits in health care, these countries initiated a public discourse on resource allocation in health care and established national committees to develop methods for the prioritisation of health care services. In most countries, priorities were implemented by practice guidelines defining clinical indications for medical interventions. In addition to this explicit allocation of scarce health care resources most countries also rely on implicit cost-containment measures (e.g., prospective reimbursement systems). Finally the article will highlight the conclusions that may be drawn from these international experiences for the German health care system. PMID- 19476307 TI - [The practice of prioritising--using the example of the Swedish cardiology guideline]. AB - In the Swedish priority guidelines, as opposed to traditional guidelines issued by professional associations, measures (in terms of condition-treatment pairs) of prevention, diagnosis, treatment and rehabilitation of cardiovascular diseases are assigned a priority value of 1 (high priority) through 10 (low priority). In its recent 2008 version this list also comprises procedures that should not be performed and those that should only be performed in the context of research projects. The government commissions the development of this list which will then be elaborated by a multi-professional team under the supervision of the National Board of Health and Welfare. In addition to scientific evidence, the prioritylists incorporate ethical and economical aspects. Examples from the Swedish guidelines will be discussed. The impact and limits of the priority lists will be described. PMID- 19476308 TI - [Post-utilitarianism and the Prioritisation Debate]. AB - Pure utilitarianism has come to be a rare position in the ethics of health resource allocation. Most authors favour a combination of a utility-maximising criterion with other criteria, notably fairness-related ones. Classical utilitarianism, though, claimed to be a moral theory that is already fair by itself. Trying to combine a utilitarian starting point with fairness-related ideas originating from anti-utilitarian criticism may result in inconsistent axiologies. The article is a report of discussions arguing the point. PMID- 19476309 TI - [General legal conditions for prioritisation within the scope of the German Statutory Health Insurance system]. AB - In setting health care priorities the law, and in particular the constitution, has to be obeyed. The social constitutional state must guarantee minimum access to health care. Members of the Statutory Health Insurance (SHI) shall have access to health care services protecting their life and ensuring their participation in society. They shall not be discriminated according to gender, race and ethnic origin, language, disability, age and sexual orientation. Essential decisions will have to be made by the legislator. Within the EC the right to access health care services in another EC member state may be an obstacle to prioritisation on the national level, e.g., to waiting lists. The exclusion of health care services on the basis of the social security law may be too simplistic an approach. Administrative discretion needs priorities, but it is unclear whether these are set to meet political priorities and real needs. The decisions of the Federal Joint Committee (Gemeinsamer Bundesausschuss) are sophisticated enough but have to respect the rule of law. There are deficits in research on the prioritisation effects of health care law. Diminishing these deficits is a prerequisite for turning political priorities into effective legal provisions. PMID- 19476310 TI - [Criteria for prioritisation from a societal perspective]. AB - The precarious financial situation of the German public health care system requires the limitation of health care benefits. Determining priorities between groups of patients, indications, or procedures and implementing preferential treatments is one of the pressing issues in health ethics, health law, social medicine and health politics. Although a public debate on priority setting, or prioritisation, has repeatedly been called for, it was mainly the physicians' views and values as well as the interests of their sponsors that have been voiced; the perspectives of patients and the public has been deemed irrelevant. In the following, we summarise the prioritisation experiences from some foreign countries and report on preliminary results obtained from qualitative interviews with healthy German citizens concerning their views on setting priorities with respect to diseases, therapies, people's lifestyle, demographic factors, and economic and ethical aspects. PMID- 19476311 TI - [Health economics: in search of efficiency]. AB - Economic terms such as efficiency, optimality and social welfare carry strong positive connotations. Sometimes non-economists may overlook the substantive difference between the scientific definition of these terms and their use in common parlance. This difference will be highly relevant if and when economic statements about efficiency are presented or interpreted in a normative way, i.e., implying that efficiency equals social desirability. Any statement about efficiency rests on implicit or explicit assumptions concerning the appropriate effectiveness criterion because efficiency invariably is an instrumental or secondary objective only, subject to clarification of the primary objectives to be pursued. In the absence of an agreement on the primary objectives of a collectively funded health scheme, the pursuit of efficiency may lead to health care allocation decisions that are not in line with prevailing social value judgements. Therefore, exposition and acceptance of the specific value judgements underlying economic evaluations of health care programmes should be a prerequisite to any attempt towards their normative interpretation. As regards the implementation of cost benefit evaluation in health care, the cautious stance taken by the German Institute for Quality and Efficiency in Health Care (IQWiG) appears to be well justified in the absence of such a fundamental consensus, especially when these evaluations are meant to address issues of allocative efficiency. PMID- 19476312 TI - [First help at the onset of shock and epilepsy]. PMID- 19476313 TI - Uncommon regioselectivity in thiacalix[4]arene formylation. AB - To reveal the alternative ways for upper-rim thiacalixarene derivatization, the formylation reactions (Gross and/or Duff conditions) of the corresponding tetrapropoxythiacalix[4]arene immobilized in the 1,3-alternate conformation were systematically studied. Surprisingly, albeit using an excess of the formylation agent, only two formyl groups were introduced exclusively into the meta positions of thiacalixarene skeleton. Unexpected regioselectivity of these reactions opens the door for a unique substitution pattern in thiacalixarene chemistry. The formation of meta-substituted aldehydes is another illustration showing remarkably different reactivity of the thiacalix[4]arene system compared with that of a classical calyx[4]arene analogue. PMID- 19476314 TI - Hydrolysis and photolysis of 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1 one, a model anti-tumor quinol ester. AB - 4-Acetoxy-4-(benzothiazol-2-yl)-2,5-cyclohexadien-1-one, 1, a quinol derivative that exhibits significant anti-tumor activity against human breast, colon, and renal cancer cell lines, undergoes hydrolysis in aqueous solution to generate an oxenium ion intermediate, 3, that is selectively trapped by N(3)(-) in an aqueous environment. The 4-(benzothiazol-2-yl) substituent slows the rate of ionization of 1 compared to analogues with 4-phenyl or 4-(p-tolyl) substituents, 4a or 4b. However, once generated, 3 is somewhat more selective than the 4-phenyl substituted cation 5a. Calculations performed at the B3LYP/6-31G(d) level agree that the 4-(benzothiazol-2-yl) substituent does significantly stabilize 3. The structure of the major isolated azide adduct, 4-(6-azidobenzothiazol-2-yl)phenol, 9, confirms that the positive charge is highly delocalized in 3. The results of hydrolysis of 1 show that the 4-(benzothiazol-2-yl) substituent has a significant inductive electron-withdrawing effect as well as a significant resonance effect that is electron-donating. Photolysis of 1 in aqueous solution generates the quinol 2 as one of several photolysis products. The presence of the quinol suggests that photolysis also leads, in part, to generation of 3, but photoionization of 1 is significantly less efficient than is the case for the esters 4a and 4b. This study proves that 3 is generated by ionization of 1 in an aqueous environment. A significant number of other 2-benzothiazole derivatives that are not quinols, including ring-substituted derivatives of 2-(4 aminophenyl)benzothiazole 15, are under development as anti-tumor agents as well. The possible generation of the reactive intermediate 17 by hydrolysis of the putative metabolite 16 is under investigation. PMID- 19476315 TI - Molecular dynamics simulations of film rupture in water/surfactant systems. AB - Molecular dynamics simulation has been performed on water/surfactant film rupture in order to investigate foam stability. A periodic boundary film model which was simulated in a lateral dimension of 8 x 8 nm(2) for 4 ns was established to stand for a part of a foam bubble. On the basis of critical film thickness, which is the lowest thickness before film rupture, a stability index was calculated to describe the capabilities of surfactants to stabilize water films. We investigated the influence of film size and simulation duration on the critical thickness and proved that our model is reasonable. The stability index versus surfactant concentration curve suggests that the capabilities of three surfactants-linear alkylbenzene sulfonate (LAS), sodium dodecyl sulfate (SDS), and heptaethylene glycol monododecyl ether (C(12)E(7))-in stabilization of water film decrease in the order of SDS > LAS > C(12)E(7). In the present study, the simulated results have been validated by the foam generation and decay experiment results, thus indicating that this method of predicting the stability of water/surfactant film is feasible. PMID- 19476316 TI - Zn(5)Sb(4)In(2-delta) - a ternary derivative of thermoelectric zinc antimonides. AB - Zn(5)Sb(4)In(2-delta) (delta = 0.15(3)) was synthesized in the form of millimeter sized crystals from reaction mixtures containing excess zinc. The ternary intermetallic compound is temperature polymorphic, and at room temperature it crystallizes with a new structure type in the orthorhombic space group Pbcn, where a = 7.1619(2), b = 17.1562(4), c = 8.6887(4) A, V = 1067.6(1) A(3), and Z = 4. The structure features 3(2)434 nets of Sb atoms that are stacked in antiposition to yield layers of square antiprisms sharing edges plus intervening tetracapped tetrahedra (tetreadersterns). The majority of Zn atoms occupy peripheral tetrahedra of such tetraedersterns, and attain at the same time the peculiar five-coordination by one like atom and four Sb atoms typical for the structures of binary zinc antimonides. The In and remaining Zn atoms are distributed in the tetragonal channels formed by the square antiprisms and display some disorder. At temperatures below 200 K Zn(5)Sb(4)In(2-delta) undergoes a phase transition into a more ordered structure with monoclinic symmetry (P2(1)/c) without any change of the unit cell. The thermoelectric properties of Zn(5)Sb(4)In(2-delta) were measured between 10 and 350 K. Exceptionally low thermal conductivity values (1 W/mK range) were obtained in the whole temperature range. Resistivity and thermopower values are characteristic of a heavily doped or degenerate semiconductor (2.5 mOmega cm and 160 muV/K, respectively, at room temperature) and show a discontinuity around 220 K. The thermoelectric figure of merit of Zn(5)Sb(4)In(2-delta) is higher than that of Zn(4)Sb(3) in the investigated temperature range. PMID- 19476317 TI - Immunolabeling and NIR-excited fluorescent imaging of HeLa cells by using NaYF(4):Yb,Er upconversion nanoparticles. AB - Upconversion fluorescent nanoparticles can convert a longer wavelength radiation (e.g., near-infrared light) into a shorter wavelength fluorescence (e.g., visible light) and thus have emerged as a new class of fluorescent probes for biomedical imaging. Rare-earth doped beta-NaYF(4):Yb,Er upconversion nanoparticles (UCNPs) with strong UC fluorescence were synthesized in this work by using a solvothermal approach. The UCNPs were coated with a thin layer of SiO(2) to form core-shell nanoparticles via a typical Stober method, which were further modified with amino groups. After surface functionalization, the rabbit anti-CEA8 antibodies were covalently linked to the UCNPs to form the antibody-UCNP conjugates. The antibody UCNP conjugates were used as fluorescent biolabels for the detection of carcinoembryonic antigen (CEA), a cancer biomarker expressed on the surface of HeLa cells. The successful conjugation of antibody to the UCNPs was found to lead to the specific attachment of the UCNPs onto the surface of the HeLa cells, which further resulted in the bright green UC fluorescence from the UCNP-labeled cells under 980 nm near-infrared (NIR) excitation and enabled the fluorescent imaging and detection of the HeLa cells. These results indicate that the amino functionalized UCNPs can be used as fluorescent probes in cell immunolabeling and imaging. Because the UCNPs can be excited with a NIR light to exhibit strong visible fluorescence and the NIR light is safe to the body and can penetrate tissue as deep as several inches, our work suggests that, with proper cell targeting or tumor-homing peptides or proteins conjugated, the NaYF(4):Yb,Er UCNPs can find potential applications in the in vivo imaging, detection, and diagnosis of cancers. PMID- 19476318 TI - Monodisperse F-substituted hydroxyapatite single-crystal nanotubes with amphiphilic surface properties. AB - Uniform F-substituted HAp nanotubes with different aspect ratios and surface properties have been successfully prepared via a hydrothermal synthetic route. A small amount of 3% F doping into HAp can lead to the formation of nanotubes. This study will provide not only novel building blocks for the construction of artificial bones or other composites with novel mechanical properties but also a new strategy for the controlled growth of inorganic nanotubes. PMID- 19476319 TI - Physicochemistry of the interaction between inulin and alkyltrimethylammonium bromides in aqueous medium and the formed coacervates. AB - Inulin, a polydisperse reserve polysaccharide, has prospective uses in food, pharmacy, and industry. Its uses and applications often encounter interactions with lipids and amphiphiles. Reports on such interactions are scarcely found in literature. In the present study, we have examined the nature of interactions between inulin and cationic amphiphiles, alkyltrimethylammonium bromides (CnTAB: n=12, 14, 16, 18), over a fair range of concentrations for both the polymer and the amphiphile. At low concentration, small induced amphiphile aggregates form complexes with inulin; at moderate concentration, the complexed inulin self aggregates leading to coacervate formation, and at higher concentration, the amphiphile forms free micelles in solution. Tensiometric, conductometric, viscometric, and turbidimetric methods have been employed to study the above phenomena. The isolated coacervates of inulin with C18TAB were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), thermogravimetry (TG), and differential thermal analysis (DTA) to ascertain their morphology, structure, and thermal stability. PMID- 19476320 TI - Heterocycle formation via palladium-catalyzed intramolecular oxidative C-H bond functionalization: an efficient strategy for the synthesis of 2 aminobenzothiazoles. AB - N-arylthioureas are converted to 2-aminobenzothiazoles via intramolecular C-S bond formation/C-H functionalization utilizing an unusual cocatalytic Pd(PPh(3))(4)/MnO(2) system under an oxygen atmosphere at 80 degrees C. This method eliminates the need for an ortho-halo substituted precursor, instead achieving direct functionalization of the ortho-aryl C-H bond. Mechanistic observations, including a large intramolecular primary kinetic isotope effect of 5.9, reveal a reaction pathway inconsistent with an electrophilic palladation mechanism. PMID- 19476321 TI - Ab initio/DFT/GIAO-CCSD(T) calculational study of the t-butyl cation: comparison of experimental data with structures, energetics, IR vibrational frequencies, and 13C NMR chemical shifts indicating preferred C(s) conformation. AB - The C(s) conformation of the tert-butyl cation 3 was established to be the preferred global energy minimum using a combination of ab initio, DFT, and CCSD(T) methodology with correlation-consistent basis sets. The potential energy surface of methyl rotation involving the C(3v), C(s), and C(3h) forms, however, in accord with previous studies, is quite flat. The computed IR absorptions of 3 indicate that it has the greatest degree of electron donation from C-H bonds into the C(+)-C bonds. The experimental (13)C NMR chemical shifts also agree very well with the experimental data. PMID- 19476322 TI - Vibration-rotation-tunneling levels of the water dimer from an ab initio potential surface with flexible monomers. AB - The 12-dimensional ab initio potential for the water dimer with flexible monomers from Huang et al. (J. Chem. Phys. 2008, 128, 034312) was used in accurate calculations of the vibration-rotation-tunneling (VRT) levels of (H2O)2 and (D2O)2 involving the intermolecular rovibrational and tunneling states as well as the intramolecular vibrations. For the intermolecular VRT levels we used a 6 + 6d model in which the fast intramolecular vibrations are adiabatically separated from the much slower intermolecular vibrations, tunneling motions, and overall rotations. We also tested two six-dimensional (6d) rigid monomer models in which the monomers were frozen either at their equilibrium geometry or at their ground state vibrationally averaged geometry. All the results from the 6 + 6d model agree well with the large amount of detailed experimental data available from high-resolution spectroscopy. For most of the parameters characterizing the spectra the results of the two 6d rigid monomer models do not significantly differ from the 6 + 6d results. An exception is the relatively large acceptor tunneling splitting, which was the only quantity for which the 6d model with the monomers frozen at their equilibrium geometry was not in good agreement with the experimental data. The 6d model with monomers at their vibrationally averaged geometry performs considerably better, and the full 6 + 6d results agree with the measurements also for this quantity. For the excited intramolecular vibrations we tested two 6 + 6d models. In the first model the excitation was assumed to be either on the donor in the hydrogen bond or on the acceptor, and to hop from one monomer to the other upon donor-acceptor interchange. In the second model the monomer excitation remains localized on a given monomer for all dimer geometries. Almost the same frequencies of the intramolecular vibrations were found for the two models. The calculations show considerable variations in the frequencies of the intramolecular modes for transitions involving different tunneling levels and different values of the rotational quantum number K. For K = 0 --> 0 transitions these variations largely cancel, however. A comparison with experimental data is difficult, except for the acceptor asymmetric stretch mode observed in high resolution spectra, because it is not clear how much the different transitions contribute to the (unresolved) peaks in most of the experimental spectra. The large red shift of the donor bound OH stretch mode is correctly predicted, but the value calculated for this red shift is too small by more than 20%. Also in the smaller shifts of the other modes we find relatively large errors. It is useful, however, that our detailed calculations including all ground and excited state tunneling levels provide an explanation for the splitting of the acceptor asymmetric stretch band observed in He nanodroplet spectra, as well as for the fact that the other bands in these spectra show much smaller or no splittings. PMID- 19476324 TI - Gas-phase protonation thermochemistry of glutamic acid. AB - Proton affinity, PA(Glu), and protonation entropy (i.e., the difference Delta(p)S(o)(Glu) = S(o)(GluH(+)) - S(o)(Glu)) of glutamic acid have been experimentally determined by the extended kinetic method using electrospray ionization triple quadrupole-time-of-flight (ESI-Q-TOF) tandem mass spectrometry. The values deduced from these experiments are PA(Glu) = 945.3 +/- 2.8(5.8) kJ x mol(-1) and Delta(p)S(o)(Glu) = -28 +/- 4(9) J x mol(-1) x K(-1) thus leading to a gas-phase basicity, GB(Glu), of 904.4 +/- 3.0(6.4) kJ x mol(-1) (uncertainties are standard deviation and, in parentheses, 95% confidence limit). Theoretical calculations performed at the G3MP2B3 level provide information on the structures, conformations, and energetics of the neutral and protonated species. Thermochemical data are calculated at this level and include a correction to the computation of the entropy associated with hindered rotation. When the lowest energy conformers of protonated and neutral glutamic acid are considered the following values are calculated: PA(Glu) = 948.1 kJ x mol(-1) and Delta(p)S(o)(Glu) = -31.3 J x mol(-1) x K(-1). Using G3MP2B3 data to estimate the gas-phase distribution of conformers at 298 K, the averaged molar quantities becomes PA(Glu) = 949.8 kJ x mol(-1) and Delta(p)S(o)(Glu) = -36.0 J x mol(-1) x K(-1). Both computations give comparable GB(Glu) = 906.4-906.7 kJ x mol(-1). PMID- 19476325 TI - Bronsted acidity of substrates influences the outcome of passerini three component reactions. AB - Passerini three-component reactions of aldehydes, isocyanides, and strong carboxylic acids (i.e., pK(a) < 2) yield alpha-acyloxycarboxamides and/or alpha acylaminocarboxamides, the characteristic products of Ugi four-component reactions. We propose that alpha-acylaminocarboxamide formation with these substrates is a consequence of in situ Bronsted acid-catalyzed reaction of the isocyanide and aldehyde to yield an imine that participates in an Ugi-type reaction. The apparent transfer of the isocyanide alpha-carbon to protic solvents as a formyl group during imine formation is indicative of new isocyanide reactivity. PMID- 19476323 TI - Construction of coordination-driven self-assembled [5 + 5] pentagons using metal carbonyl dipyridine ligands. AB - The coordination-driven self-assembly of two metal-carbonyl-cluster-coordinated dipyridyl donors, (4-C(5)H(4)N)(2)C[triple bond]CCo(2)(CO)(6) (1) and (4 C(5)H(4)N)(2)C[triple bond]CMo(2)Cp(2)(CO)(4) (2), with a linear diplatinum(II) acceptor ligand was investigated. The structures of the resulting self-assembled polygons were found to be controlled by the steric bulk of the metal-carbonyl cluster adduct. The use of a sterically less imposing ligand 1 resulted in a pentagon-hexagon mixture, which was characterized by electrospray ionization time of-flight mass spectroscopy. The exclusive formation of a [5 + 5] pentagon was achieved by the self-assembly of the bulkier molybdenum donor ligand 2 with a linear organoplatinum(II) acceptor ligand. Molecular force field modeling was used to study the structural details of the pentagonal and hexagonal architectures. The first Fe(3)-Co(6)-Pt(6) trimetal [3 + 3] hexagon was also synthesized via the combination of 1 with a 120 degrees ferrocenyldiplatinum(II) acceptor. PMID- 19476327 TI - An efficient CuCN-catalyzed synthesis of optically active 2,3-allenols from optically active 1-substituted 4-chloro-2-butyn-1-ols. AB - The sequential treatment of optically active terminal propargylic alcohols with n BuLi/(HCHO)(n) and regioselective chlorination afforded the corresponding optically active 4-chloro-2-butyn-1-ols. With R(1) being a methyl or an ethyl group, an alternative for the synthesis of the corresponding optically active propargylic alcohols is the Novozym 435-catalyzed kinetic resolution of these racemic 4-chloro-2-butyn-1-ols. The subsequent reaction of these optically active 4-chloro-2-butyn-1-ols with the corresponding Grignard reagents under the catalysis of 5 mol % of CuCN afforded the optically active secondary 2,3-allenols in good yields with up to >99% ee. PMID- 19476326 TI - Protected cyanohydrins in the synthesis of rotenoids: (+/-)-munduserone and (+/-) cis-12a-hydroxymunduserone. AB - Short synthetic routes to the natural products (+/-)-munduserone 1 and (+/-)-cis 12a-hydroxymunduserone 9 from protected cyanohydrin 5 and nitrochromene 4 are described. The key coupling reaction of 4 and 5 gave under inverse addition conditions 9 (28%) and 2b (21%), while under normal addition conditions, a mixture of 9 (20%), dehydromunduserone 10 (9%), and enone 2b (10%) was obtained. (+/-)-Munduserone 1 is easily obtained from both 2b and 9 by 10% methanolic HCl (86%) and Zn/AcOH (71%) treatments, respectively. PMID- 19476328 TI - Copper(I)-catalyzed aryl bromides to form intermolecular and intramolecular carbon-oxygen bonds. AB - A highly efficient Cu-catalyzed C-O bond-forming reaction of alcohol and aryl bromides has been developed. This transformation was realized through the use of copper(I) iodide as a catalyst, 8-hydroxyquinoline as a ligand, and K(3)PO(4) as a base. A variety of functionalized substrates were found to react under these reaction conditions to provide products in good to excellent yields. PMID- 19476329 TI - Preparation of photoactivable amino acid derivatives. AB - A range of N-protected-alpha-amino acyl-5,7-dinitroindolines 3a-z were prepared in good yields from commercially available N-protected-alpha-amino acids 1a-z by a two-step sequence of acylation and intramolecular amide N-arylation. Subsequent photochemical acylation of the N-protected-alpha-amino acyl-5,7-dinitroindolines 3e,g,r afforded the corresponding N-protected-alpha-amino acid amides 22e,g,r (77 92%) under mild conditions. All these reactions occurred with complete retention of chirality as evidenced by NMR analysis. This scheme provides an attractive and alternative method to the conventional acylation of alpha-amino acids, especially in cases where the amide bond needs to be formed without the use of a coupling reagent. PMID- 19476330 TI - Structural effects on the catalytic, emulsifying, and recycling properties of chiral amphiphilic dendritic organocatalysts. AB - Three series of chiral amphiphilic G1-G3 dendritic organocatalysts containing an optically active polar proline-derived core and one or two nonpolar hydrocarbon dendrons were prepared. These dendritic organocatalysts were employed in the asymmetric aldol and nitro-Michael additions in oil-in-water emulsions to reveal the effects of dendron size and branching on the catalytic properties. The incorporation of larger hydrophobic dendrons has the advantages of promoting emulsion formation in water, improving the reaction enantioselectivity, decreasing catalyst loading (to 1 mol %), and facilitating catalyst recovery after the reactions. In general, the larger dendrons tended to lower catalyst reactivity due to their increasing steric blocking effect. However, some astonishing observations were found in some of the G1 and G2 dendritic organocatalysts, wherein an increase in the steric bulkiness and branching of the dendron resulted in better catalyst reactivity. It was also found that higher product yields and enantioselectivities were obtained in the aldol reactions when the aromatic aldehyde contains an electron-withdrawing substituent. The catalysts could be recycled and reused five times without significant drop in product yields and enantioselectivities. In addition, cross product contamination was not found when the recovered G3 catalyst was subsequently used in another reaction involving different substrates. PMID- 19476332 TI - Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. AB - The combination of nanotechnology and molecular biology has developed into an emerging research area: nanobiotechnology. Magnetic nanoparticles are well established nanomaterials that offer controlled size, ability to be manipulated externally, and enhancement of contrast in magnetic resonance imaging (MRI). As a result, these nanoparticles could have many applications in biology and medicine, including protein purification, drug delivery, and medical imaging. Because of the potential benefits of multimodal functionality in biomedical applications, researchers would like to design and fabricate multifunctional magnetic nanoparticles. Currently, there are two strategies to fabricate magnetic nanoparticle-based multifunctional nanostructures. The first, molecular functionalization, involves attaching antibodies, proteins, and dyes to the magnetic nanoparticles. The other method integrates the magnetic nanoparticles with other functional nanocomponents, such as quantum dots (QDs) or metallic nanoparticles. Because they can exhibit several features synergistically and deliver more than one function simultaneously, such multifunctional magnetic nanoparticles could have unique advantages in biomedical applications. In this Account, we review examples of the design and biomedical application of multifunctional magnetic nanoparticles. After their conjugation with proper ligands, antibodies, or proteins, the biofunctional magnetic nanoparticles exhibit highly selective binding. These results indicate that such nanoparticles could be applied to biological medical problems such as protein purification, bacterial detection, and toxin decorporation. The hybrid nanostructures, which combine magnetic nanoparticles with other nanocomponents, exhibit paramagnetism alongside features such as fluorescence or enhanced optical contrast. Such structures could provide a platform for enhanced medical imaging and controlled drug delivery. We expect that the combination of unique structural characteristics and integrated functions of multicomponent magnetic nanoparticles will attract increasing research interest and could lead to new opportunities in nanomedicine. PMID- 19476331 TI - Integrin alphaVbeta3 targeted gene delivery using RGD peptidomimetic conjugates with copolymers of PEGylated poly(ethylene imine). AB - This study describes the synthesis and characterization of five conjugates of poly(ethylene glycol) modified polyethylenimine (PEG-PEIs) coupled in two different synthesis routes to a nonpeptidic pentacyclic RDG-mimetic for integrin receptor-targeted gene delivery. Synthesis of this panel of different conjugates allowed for systematic analysis of structure-activity relationships. Conjugates were therefore characterized regarding molecular composition, DNA condensation, size, and zeta potential of self-assembled polyplexes. In vitro characterization included investigation of blood compatibility, binding affinity to receptor positive and receptor-negative cells measured by flow cytometry, cellular uptake quantified by scintillation counting, and efficiency and specificity of transfection assayed by reporter gene expression. In a first synthetic approach, low molecular weight PEI (LMW-PEI) was PEGylated using a heterobifunctional PEG linker and coupling of the RGD-mimetic was achieved at the distal end of PEG chains. In a second synthesis route, the RGD-mimetic was directly coupled to AB block-copolymers of PEI (25 kDa) and PEG (30 kDa). Interactions of RGD-PEG-LMW PEI conjugates with DNA were strongly impaired, whereas PEG-PEI-RGD conjugates were more promising candidates due to their physicochemical properties and higher receptor specificity. The binding, uptake, and transfection efficiency in receptor-positive cells was strongly increased upon conjugation of the RGD mimetic to AB-block-copolymers of PEG-PEI and depended on the degree of peptide substitution. The conjugates of PEG-PEI AB-block-copolymers with low ligand density of the RGD-mimetic appear to be promising candidates for in vivo cancer gene therapy. PMID- 19476333 TI - H-bonding as a control element in stereoselective Ru-catalyzed olefin metathesis. AB - H-bonding interactions have been exploited extensively in the design of catalysts for stereoselective synthesis but have rarely been utilized in the development of metal-catalyzed processes. Studies described herein demonstrate that intramolecular H-bonding interactions can significantly increase the rate and levels of stereochemical control in Ru-catalyzed olefin metathesis reactions. The utility of H-bonding in catalytic olefin metathesis is elucidated through development of exceptionally facile and highly diastereoselective ring opening/cross-metathesis (DROCM) reactions, involving achiral Ru catalysts and enantiomerically enriched allylic alcohols. Transformations proceed to completion readily (> 98% conversion, up to 87% yield), often within minutes, in the presence of < or = 2 mol % of an achiral catalyst to afford synthetically versatile products of high stereochemical purity (up to > 98:2 dr and 11:1 E:Z). PMID- 19476334 TI - Microcontact deprinting: a technique to pattern gold nanoparticles. AB - A simple and general patterning technique for inorganic nanoparticles (NPs, e.g., gold NPs) is demonstrated, consisting of the selective lift-off of metal precursor loaded block copolymer micelles. The procedure works as follows: first, a topographically micropatterned polystyrene (PS) stamp is placed in contact with a substrate covered with hexagonally arranged micelles. Then the assembly is heated above the glass transition temperature (T(g)) of PS, and finally, the PS stamp is peeled off, removing from the substrate the micelles that were in contact with the protrusions of the stamp. As a result, patterns of micelles either exactly identical to the original or with much smaller features down to submicrometer were obtained. In a subsequent step, the organic material can be removed and the metal precursor reduced by plasma treatment, resulting in patterns of NPs. This technique, denoted as "micro-contact deprinting", provides a fast and inexpensive way to obtain hierarchical patterns of NPs on a wide range of substrates. It is demonstrated that it can even be applied on curved surfaces because of the softness of the PS stamp above its T(g). PMID- 19476335 TI - Metabonomic evaluation of melamine-induced acute renal toxicity in rats. AB - The recent outbreak of renal failure in infants in China has been determined to be caused by melamine (Mel) and derivatives adulterated in the food. A metabonomic study was performed to evaluate the global biochemical alteration triggered by Mel ingestion in parallel with the acute renal toxicity in rats. Mel at 600, 300, and 100 mg/kg, cyanuric acid (Cya) at 100 mg/kg, and mixture of Mel and Cya (50 mg/kg each) were administered in five groups of Wistar rats, respectively, via oral gavage for 15 days. Urinary metabonomic profiles indicated that Mel perturbed urinary metabolism in a dose-dependent manner, with high-dose group showing the most significant impact. Metabonomic variations also suggest that the toxicity of low-dose (50 mg/kg) Mel was greatly elevated by the presence of Cya (at 50 mg/kg), which was able to induce a significant metabolic alteration to a level equivalent to that of 600 mg/kg Mel. Histological examination and serum biochemical analysis also indicated that the low-dose Mel-Cya mixture and high-dose Mel group resulted in the greatest renal toxicity. The high-dose Mel and low-dose Mel-Cya resulted in disrupted amino acid metabolism including tryptophan, polyamine, and tyrosine metabolism, and altered TCA and gut microflora structure. PMID- 19476336 TI - Chemical constituents from the aerial parts of Artemisia minor. AB - Four new compounds including three bicoumarins, arteminorins A-C (1-3), and one neolignan, arteminorin D (4), together with 31 known ones were isolated from the aerial parts of Artemisia minor. Their structures were established on the basis of spectroscopic data and comparison with those of the related known compounds. Ethyl caffeate (27) showed in vitro cytotoxicity against the HepG2 cancer cell line. Arteminorin C (3) and luteolin (19) showed inhibitory activity on xanthine oxidase (XOD), and caffeic acid (28) exhibited inhibitory activity on protein tyrosine phosphatase 1B (PTP1B). PMID- 19476337 TI - Characterization of an aldolase-dehydrogenase complex that exhibits substrate channeling in the polychlorinated biphenyls degradation pathway. AB - An aldolase and dehydrogenase complex from the polychlorinated biphenyl degradation pathway of the bacterium Burkholderia xenovorans LB400 was purified. The aldolase, BphI, had the highest activity with Mn(2+) as the cofactor and was able to transform 4-hydroxy-2-oxopentanoate and 4-hydroxy-2-oxohexanoate to pyruvate and acetaldehyde or propionaldehyde with similar specificity constants. Aldolase activity was competitively inhibited by the pyruvate enolate analogue, oxalate, with a K(ic) of 0.93 microM. The pH-rate profiles suggested the involvement of a pK(a) 7.7 catalytic base in the reaction mechanism. BphI activity was activated 15-fold when substrate turnover was occurring in the dehydrogenase, BphJ, which can be attributed partially to nicotinamide coenzyme binding to BphJ. BphJ had similar specificity constants for acetaldehyde or propionaldehyde and was able to utilize aliphatic aldehydes from two to five carbons in length as substrates, although K(m) values for these aldehyes were >20 mM. When 4-hydroxy-2-oxopentanoate was provided as a substrate to the BphI-BphJ complex in a coupled enzyme assay, no lag in the progress curve of BphJ was observed. When 1 mM propionaldehyde was added exogenously to a reaction mixture containing 0.1 mM 4-hydroxy-2-oxopentanoate, 95% of the CoA esters produced was acetyl CoA. Conversely, 99% of the CoA esters produced was propionyl CoA when a 10-fold molar excess of exogenous acetaldehyde was added in a reaction mixture containing 4-hydroxy-2-oxohexanoate. These results demonstrate that acetaldehyde and propionaldehyde, products of the BphI reaction, are not released in the bulk solvent but are channeled directly to the dehydrogenase. PMID- 19476338 TI - Design, synthesis and optical resolution of new bifunctional ligand: 1,1' dimethyl-octahydro-8,8'-biquinoline-7,7'-diol. AB - The design, synthesis and optical resolution of a new bifunctional ligand, 1,1' dimethyl-octahydro-8,8'-biquinoline-7,7'-diol, is described. This new aza analogue of BINOL exhibits different properties as compared to BINOL. PMID- 19476339 TI - Hyaluronic acid-quantum dot conjugates for in vivo lymphatic vessel imaging. AB - A simple and novel electrostatic coupling method is reported, which provides a hyaluronic acid-quantum dot conjugate (HA-QD) that is colloidally stable and size tunable from 50 to 120 nm. The HA-QDs show cancer targeting efficiency, which suggests diagnostic and imaging applications. The conjugates are also demonstrated for the fluorescence staining capability for lymphatic vessels in vitro and in vivo. Using the HA-QDs in a small animal model, lymphatic vessels are visualized real-time in vivo for days. Comprehensive cytotoxicity evaluations are made for the conjugates and the unconjugated counterpart. The HA-QDs showcase the potentials toward cancer imaging and real-time visualization of changes in lymphatic vessels such as lymphangiogenesis. PMID- 19476340 TI - Hop (Humulus lupulus)-derived bitter acids as multipotent bioactive compounds. AB - Hop acids, a family of bitter compounds derived from the hop plant (Humulus lupulus), have been reported to exert a wide range of effects, both in vitro and in vivo. They exhibit potential anticancer activity by inhibiting cell proliferation and angiogenesis, by inducing apoptosis, and by increasing the expression of cytochrome P450 detoxification enzymes. Furthermore, hop bitter acids are effective against inflammatory and metabolic disorders, which makes them challenging candidates for the treatment of diabetes mellitus, cardiovascular diseases, and metabolic syndrome. This review summarizes the current knowledge on hop bitter acids, including both phytochemical aspects, as well as the biological and pharmacological properties of these compounds. PMID- 19476341 TI - Unprecedented degradation of nickel(II) 2,3,12,13-tetrabromo-5,10,15,20 tetraarylporphyrins by the anion of E-benzaldoxime: a novel approach to nickel(II) chlorophins and bacteriophins. AB - A novel and convenient approach to chlorophins and bacteriophins has been developed through a degradation of nickel(II) 2,3,12,13-tetrabromo-5,10,15,20 tetraarylporphyrins by the anion of E-benzaldoxime. The UV-vis spectra of these chlorophins and bacteriophins are similar to those of metalated chlorin and bacteriochlorin systems but with more intense and bathochromically shifted Q bands. PMID- 19476342 TI - Diffusion of nanoparticles in semidilute and entangled polymer solutions. AB - We studied the diffusion of gold nanoparticles in semidilute and entangled solutions of polystyrene (PS) in toluene using fluctuation correlation spectroscopy (FCS). The polymer concentration was varied from approximately 6c* to 20c*, where c* is the overlap concentration. In our experiments, the particle radius (R approximately 2.5 nm) was much smaller compared to the radius of gyration (Rg approximately 18 nm) of the chain but comparable to the average mesh size (xi) of the fluctuating polymer network. The diffusion coefficient (D) of the particles decreased monotonically with polymer concentration and it can be fitted with a stretched exponential function, D=D0 exp(-microcnu), with the value of the scaling parameter, nu approximately 0.9. At high concentration of the polymer, a clear subdiffusive motion of the particles was observed. The results were compared with the diffusion of free dyes (coumarin 480), which showed normal diffusive behavior for all concentrations. PMID- 19476344 TI - Capillary and microfluidic gradient elution isotachophoresis coupled to capillary zone electrophoresis for femtomolar amino acid detection limits. AB - In this work, gradient elution isotachophoresis was combined with capillary zone electrophoresis (GEITP-CZE) in a single microcolumn. The multistage approach addresses the issues of analyte resolution difficulties in GEITP, as well as poor concentration sensitivity in CZE. GEITP employs rapid electrophoretic focusing at a discontinuous ionic interface within a sample well generated through combined electroosmotic and hydrodynamic flows. The interface and enriched analytes are then pulled into a capillary or microchannel as the counter-flow is reduced for on-column detection. To transform GEITP-focused samples to CZE-based separation, the sample solution is replaced with CZE buffer solution while maintaining hydrodynamic flow to ensure migration toward the detector. The single solution switch and lack of polarity inversion allows for reproducible separations (typically <6% relative standard deviation in peak heights and <0.5% in migration times). Low-pressure hydrodynamic flow during CZE allowed for flexible resolution adjustment, with a linear increase versus the square root of migration time, without altering the separation column, field strength, or electrolyte system. As a first demonstration of the applicability of GEITP-CZE, a series of amino acids to be assayed for in future Mars exploration missions as indicators of biological life were studied. Separation of six amino acids, with limits of detection as low as 200 fM, were achieved using a capillary format with a total analysis time of 11 min. A glass-based microfluidic implementation is also demonstrated that can perform GEITP-CZE in 1 cm effective lengths. PMID- 19476343 TI - Diffusion-driven device for a high-resolution dose-response profiling of combination chemotherapy. AB - Combination therapies have proven vital in the fight against HIV and cancer. However, the identification and optimization of such combination therapies is largely experience driven and an activity of clinicians rather than of systematic screening efforts. Here we present a diffusion device, compatible with the format of a 12-well microtiter plate, to create and test all possible mixtures of two substances with only two pipetting steps. Applications to the testing of different drug combinations and the parallel screening of different leukemia cell lines as well as primary patient cells are presented. The diffusion device yields qualitatively and quantitatively comparable results to an MTT viability assay conducted in a standard 96-well format albeit with a tremendous reduction of processing steps. In addition, a fluorescence-based annexin V binding assay of cell death was implemented. Next to the reduction of processing steps, the diffusion device constitutes a considerable assay miniaturization that overcomes the problems typically associated with miniaturization as a consequence of small sample volumes. Given its ease of handling, the device will greatly advance the development and optimization of combination drugs and the identification of optimum drug combinations in personalized medicine. PMID- 19476345 TI - An expeditious entry to 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO): another highly active organocatalyst for oxidation of alcohols. AB - A practical, three-step synthetic route to 9-azabicyclo[3.3.1]nonane N-oxyl (ABNO, 3), an unhindered, stable class of nitroxyl radical, has been developed. ABNO exhibits a highly active nature compared with TEMPO in the catalytic oxidation of alcohols to their corresponding carbonyl compounds. PMID- 19476347 TI - Cobalt(II) sheet-like systems based on diacetic ligands: from subtle structural variances to different magnetic behaviors. AB - The preparation, X-ray crystallography, and magnetic investigation of the compounds [Co(H(2)O)(2)(phda)](n) (1), [Co(phda)](n) (2), and [Co(chda)](n) (3) [H(2)phda = 1,4-phenylenediacetic acid and H(2)chda = 1,1-cyclohexanediacetic acid] are described herein. The cobalt atoms in this series are six- (1) and four coordinated (2 and 3) in distorted octahedral (CoO(6)) and tetrahedral (CoO(4)) environments. The structures of 1-3 consists of rectangular-grids which are built up by sheets of cobalt atoms linked through anti-syn carboxylate bridges, giving rise to either a three-dimensional structure across the phenyl ring (1 and 2) or to regularly stacked layers with the cyclohexyl groups acting as organic separators (3). The magnetic properties of 1-3 were investigated as a function of the temperature and the magnetic field. Ferromagnetic coupling between the six coordinate cobalt(II) ions across the anti-syn carboxylate bridge occurs in 1 (J = +1.2 cm(-1)) whereas antiferromagnetic coupling among the tetrahedral cobalt(II) centers within the sheets is observed in 2 and 3 [J = -1.63 (2) and 1.70 cm(-1) (3)] together with a spin-canted structure in 3 giving rise a long range magnetic ordering (T(c) = 7.5 K). PMID- 19476346 TI - Glycosylated SV2 and gangliosides as dual receptors for botulinum neurotoxin serotype F. AB - Botulinum neurotoxin causes rapid flaccid paralysis through the inhibition of acetylcholine release at the neuromuscular junction. The seven BoNT serotypes (A G) have been proposed to bind motor neurons via ganglioside-protein dual receptors. To date, the structure-function properties of BoNT/F host receptor interactions have not been resolved. Here, we report the crystal structures of the receptor binding domains (HCR) of BoNT/A and BoNT/F and the characterization of the dual receptors for BoNT/F. The overall polypeptide fold of HCR/A is essentially identical to the receptor binding domain of the BoNT/A holotoxin, and the structure of HCR/F is very similar to that of HCR/A, except for two regions implicated in neuronal binding. Solid phase array analysis identified two HCR/F binding glycans: ganglioside GD1a and oligosaccharides containing an N acetyllactosamine core. Using affinity chromatography, HCR/F bound native synaptic vesicle glycoproteins as part of a protein complex. Deglycosylation of glycoproteins using alpha(1-3,4)-fucosidase, endo-beta-galactosidase, and PNGase F disrupted the interaction with HCR/F, while the binding of HCR/B to its cognate receptor, synaptotagmin I, was unaffected. These data indicate that the HCR/F binds synaptic vesicle glycoproteins through the keratan sulfate moiety of SV2. The interaction of HCR/F with gangliosides was also investigated. HCR/F bound specifically to gangliosides that contain alpha2,3-linked sialic acid on the terminal galactose of a neutral saccharide core (binding order GT1b = GD1a >> GM3; no binding to GD1b and GM1a). Mutations within the putative ganglioside binding pocket of HCR/F decreased binding to gangliosides, synaptic vesicle protein complexes, and primary rat hippocampal neurons. Thus, BoNT/F neuronal discrimination involves the recognition of ganglioside and protein (glycosylated SV2) carbohydrate moieties, providing a structural basis for the high affinity and specificity of BoNT/F for neurons. PMID- 19476349 TI - Density functional theory studies of structural deformation in bis(alkynyl)diruthenium(III): Stronger Ru-Ru bonding by any means necessary. AB - Conjugated organometallic compounds diruthenium(6+) bis(alkynyl)s exhibit an unusual structure that is severely distorted from a typical D(4) paddlewheel geometry. Density functional theory calculations suggest that the distortion is driven by both the need for an enlarged highest occupied molecular orbital-lowest unoccupied molecular orbital gap and stronger Ru-Ru bonding through the formation of partial sigma and pi bonds. PMID- 19476350 TI - Comparison of several molecular docking programs: pose prediction and virtual screening accuracy. AB - Molecular docking programs are widely used modeling tools for predicting ligand binding modes and structure based virtual screening. In this study, six molecular docking programs (DOCK, FlexX, GLIDE, ICM, PhDOCK, and Surflex) were evaluated using metrics intended to assess docking pose and virtual screening accuracy. Cognate ligand docking to 68 diverse, high-resolution X-ray complexes revealed that ICM, GLIDE, and Surflex generated ligand poses close to the X-ray conformation more often than the other docking programs. GLIDE and Surflex also outperformed the other docking programs when used for virtual screening, based on mean ROC AUC and ROC enrichment values obtained for the 40 protein targets in the Directory of Useful Decoys (DUD). Further analysis uncovered general trends in accuracy that are specific for particular protein families. Modifying basic parameters in the software was shown to have a significant effect on docking and virtual screening results, suggesting that expert knowledge is critical for optimizing the accuracy of these methods. PMID- 19476351 TI - Contribution of the closing base pair to exceptional stability in RNA tetraloops: roles for molecular mimicry and electrostatic factors. AB - Hairpins are common RNA secondary structures that play multiple roles in nature. Tetraloops are the most frequent RNA hairpin loops and are often phylogenetically conserved. For both the UNCG and GNRA families, CG closing base pairs (cbps) confer exceptional thermodynamic stability but the molecular basis for this has remained unclear. We propose that, despite having very different overall folds, these two tetraloop families achieve stability by presenting the same functionalities to the major groove edge of the CG cbp. Thermodynamic contributions of this molecular mimicry were investigated using substitutions at the nucleobase and functional group levels. By either interrupting or deleting loop-cbp electrostatic interactions, which were identified by solving the nonlinear Poisson-Boltzmann (NLPB) equation, stability changed in a manner consistent with molecular mimicry. We also observed a linear relationship between DeltaG(o)(37) and log[Na(+)] for both families, and loops with a CG cbp had a decreased dependence of stability on salt. NLPB calculations revealed that, for both UUCG and GAAA tetraloops, the GC cbp form has a higher surface charge density, although it arises from changes in loop compaction for UUCG and changes in loop configuration for GAAA. Higher surface charge density leads to stronger interactions of GC cbp loops with solvent and salt, which explains the correlation between experimental and calculated trends of free energy with salt. Molecular mimicry as evidenced in these two stable but otherwise unrelated tetraloops may underlie common functional roles in other RNA and DNA motifs. PMID- 19476352 TI - Helical vesicles, segmented semivesicles, and noncircular bilayer sheets from solution-state self-assembly of ABC miktoarm star terpolymers. AB - Multicompartment micelles, especially nanostructured vesicles, offer tremendous potential as delivery vehicles of therapeutic agents and nanoreactors. Solution state self-assembly of miktoarm star terpolymers provides a versatile and powerful route to obtain multicompartment micelles. Here we report simulations of solution-state self-assembly of ABC star terpolymers composed of a solvophilic A arm and two solvophobic B and C arms. A variety of multicompartment micelles are predicted from the simulations. Phase diagrams for typical star terpolymers are constructed. It is discovered that the overall micelle morphology is largely controlled by the volume fraction of the solvophilic A arms, whereas the internal compartmented and/or segregated structures depend on the ratio between the volume fractions of the two solvophobic arms. The polymer-solvent and polymer-polymer interactions can be used to tune the effective volume fraction of the A-arm and, thereby, induce morphological transitions. For terpolymers with equal or nearly equal length of B and C arms, several previously unknown structures, including vesicles with novel lateral structures (helices or stacked donuts), segmented semivesicles, and elliptic or triangular bilayer sheets, are discovered. When the lengths of B and C arms are not equal, novel micelles such as multicompartment disks and onions are observed. PMID- 19476353 TI - Biosynthesis of the sesquiterpene botrydial in Botrytis cinerea. Mechanism and stereochemistry of the enzymatic formation of presilphiperfolan-8beta-ol. AB - Presilphiperfolan-8beta-ol synthase, encoded by the BcBOT2 gene from the necrotrophic plant pathogen Botrytis cinerea, catalyzes the multistep cyclization of farnesyl diphosphate (2) to the tricyclic sesquiterpene alcohol presilphiperfolan-8beta-ol (3), the preursor of the phytotoxin botrydial, a strain-dependent fungal virulence factor. Incubation of (1R)-[1-(2)H]farnesyl diphosphate (2b) with recombinant presilphiperfolan-8beta-ol synthase gave exclusively (5R)-[5alpha-(2)H]-3b, while complementary incubation of (1S)-[1 (2)H]FPP (2c) gave (5S)-[5beta-(2)H]-3c. These results established that cyclization of farnesyl diphosphate involves displacement of the diphosphate group from C-1 with net inversion of configuration and ruled out the proposed intermediacy of the cisoid conformer of nerolidyl diphosphate (9) in the cyclization. While not a mandatory intermediate, (3R)-nerolidyl diphosphate was shown to act as a substrate surrogate. Cyclization of [13,13,13-(2)H(3)] farnesyl diphosphate (2d) gave [14,14,14-(2)H(3)]-3d, thereby establishing that electrophilic attack takes place exclusively on the si face of the 12,13-double bond of 2. The combined results provide a detailed picture of the conformation of enzyme-bound farnesyl diphosphate at the active site of presilphiperfolan-8beta ol synthase. PMID- 19476354 TI - Dissociation of water during formation of anodic aluminum oxide. AB - According to model computations at the B3LYP/6-311+G** level, an external electric field can facilitate the heterolytic dissociation of properly oriented water molecules significantly. Depending on the models used, the maximum predicted change of the dissociation energy in the field is ca. -3 to -4 kcal nm mol(-1) V(-1), and decreases with the cosine of the angle between the external field and the breaking OH bond. These microscopic results can be related semiquantitatively to macroscopic observables from mechanistic studies on the pore formation of anodic aluminum oxide, thus lending support to the equifield strength model and field-enhanced water dissociation at the growing oxide surface that has been put forward in these studies. PMID- 19476355 TI - Lithium salt of tetrahydroxybenzoquinone: toward the development of a sustainable Li-ion battery. AB - The use of lithiated redox organic molecules containing electrochemically active C=O functionalities, such as lithiated oxocarbon salts, is proposed. These represent alternative electrode materials to those used in current Li-ion battery technology that can be synthesized from renewable starting materials. The key material is the tetralithium salt of tetrahydroxybenzoquinone (Li(4)C(6)O(6)), which can be both reduced to Li(2)C(6)O(6) and oxidized to Li(6)C(6)O(6). In addition to being directly synthesized from tetrahydroxybenzoquinone by neutralization at room temperature, we demonstrate that this salt can readily be formed by the thermal disproportionation of Li(2)C(6)O(6) (dilithium rhodizonate phase) under an inert atmosphere. The Li(4)C(6)O(6) compound shows good electrochemical performance vs Li with a sustained reversibility of approximately 200 mAh g(-1) at an average potential of 1.8 V, allowing a Li-ion battery that cycles between Li(2)C(6)O(6) and Li(6)C(6)O(6) to be constructed. PMID- 19476356 TI - Heteroepitaxial ferroelectric ZnSnO3 thin film. AB - We investigated the ferroelectric characteristics of an epitaxial perovskite ZnSnO(3) thin film on a (111) SrRuO(3)/(111) SrTiO(3) substrate fabricated by pulsed laser deposition. We confirmed that the ZnSnO(3) thin film was epitaxially grown on the substrate, forming large terraces on the surface of the ZnSnO(3) thin film. The ZnSnO(3) thin film exhibited a high ferroelectric polarization of approximately 47 microC/cm(2), which was further supported by first-principles calculations. PMID- 19476357 TI - Direct measurement of photoinduced charge separation distances in donor-acceptor systems for artificial photosynthesis using OOP-ESEEM. AB - The distance over which two photogenerated charges are separated in electron donor-acceptor systems for artificial photosynthesis depends on the structure of the system, while the lifetime of the charge separation and, ultimately, its ability to carry out useful redox chemistry depend on the electronic coupling between the oxidized donor and reduced acceptor. The radical ions produced by charge separation are frequently delocalized over the pi systems of the final oxidized donor and reduced acceptor, so that there is often significant uncertainty as to the average distance between the separated charges, especially in low dielectric constant media, where the Coulomb attraction of the ions may be significant and the charge distribution of the ions may be distorted, so that the average distance between them may be shorter than that implied by their chemical structures. The charge separation distances between photogenerated radical ions in three donor-acceptor molecules having different donor-acceptor distances were measured directly from their dipolar spin-spin interactions using out-of-phase electron spin echo envelope modulation (OOP-ESEEM). The measured distances in toluene at 85 K compare favorably to the calculated distances between the centroids of the spin distributions of the radical ions within the radical ion pairs. These results show that despite the intrinsically nonpolar nature of medium, the spin (and charge) distributions of the RPs are not significantly distorted by Coulomb attraction over these long distances. This study shows that OOP-ESEEM is well-suited for probing the detailed structural features of charge separated intermediates that are essential to understanding how to design molecular structures that prolong and control charge separation for artificial photosynthesis. PMID- 19476358 TI - A multiscale scheme for the simulation of conformational and solution properties of different dendrimer molecules. AB - We propose a multiscale protocol for the simulation of conformation and dynamics of dendrimer molecules in dilute solution. Conformational properties (radius of gyration, mass distribution, and scattering intensities) and overall hydrodynamic properties (translational diffusion and intrinsic viscosity) are predicted by means of a very simple coarse-grained bead-and-spring model, whose parameters are not adjusted against experimental properties, but rather they are obtained from previous, atomic-level simulations which are also quite simple, performed with small fragments and Langevin dynamics simulation. The scheme is described and applied systematically to four different dendrimer molecules with up to seven generations. The predictive capability of this scheme is tested by comparison with experimental data. It is found that the predicted geometric and hydrodynamic radii of the dendrimer molecules are in agreement (typical error is about 4%) with a large set experimental values of the four dendrimers with various numbers of generations. Agreement with some X-ray scattering experimental intensities also confirms the good prediction of the internal structure. This scheme is easily extendable to study more complex molecules (e.g., functionalized dendrimers) and to simulate internal dynamics. PMID- 19476359 TI - In vitro and in vivo anti-angiogenic activities and inhibition of hormone dependent and -independent breast cancer cells by ceramide methylaminoethylphosphonate. AB - Ceramide methylaminoethylphosphonate (CMAEPn) was isolated from eastern oyster ( Crassostrea virginica ) and screened against in vitro and in vivo angiogenesis and against MCF-7 and MDA-MB-435s breast cancer cell lines. In vitro angiogenesis was evaluated by the vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) tube formation assay. MCF-7 and MDA-MB 435s cell viability was evaluated by the CellTiter 96 AQ(ueous) One Solution Cell Proliferation assay. Apoptosis was evaluated by the caspase-9 assay, autophagy by acridine orange staining and beclin-1 level. Our study indicates that CMAEPn at 50 microM inhibited VEGF-induced tube formation by HUVEC. The viability of MCF-7 and MDA-MB-435s breast cancer cells exposed to 125 microM CMAEPn for 48 h was reduced to 76 and 85%, respectively. The viability of MCF-7 and MDA-MB-435s cells exposed to 250 microM CMAEPn for 48 h under the same conditions was reduced to 38 and 45%, respectively. CMAEPn at 125 microM inhibited VEGF-induced MDA-MB-435s cell migration and invasion. CMAEPn at 125 microM also decreased VEGF, EGF levels in the conditioned media, PI3K, IkappaB phosphorylation and degradation in the cytoplasmic extracts, and NFkappaB nuclear translocation. Both acridine orange staining and beclin-1 indicated autophagic cell death in MCF-7 and MDA-MB-435s cells, respectively. In vivo, CMAEPn at 30 mg/kg body weight inhibited bFGF induced angiogenesis and caused a 57% reduction in hemoglobin levels in the matrigel plug assay within 7 days. This is the first report on CMAEPn-inhibited angiogenesis both in vitro and in vivo. PMID- 19476361 TI - Molecular structure and baking performance of individual glycolipid classes from lecithins. AB - The potential of individual glycolipid classes from lecithins (soybean, rapeseed, and sunflower) in breadmaking was determined in comparison to classical surfactants such as diacetyltartaric acid esters of mono- and diacylglycerides (DATEM), monoacylglycerides, sodium stearoyl-2-lactylate (SSL), and two synthetic glycolipids by means of rheological and baking tests on a microscale. A highly glycolipid-enriched sample containing the entire glycolipid moiety of the lecithin was obtained using an optimized batch procedure with silica gel. This sample was subsequently used to gain individual glycolipid classes through column chromatography on silica gel. The major glycolipid classes in the lecithins, digalactosyl diacylglycerides (1), sterol glucosides (2), acylated sterol glucosides (3), and cerebrosides (4), were identified and characterized. All isolated glycolipid classes displayed excellent baking performance. A better baking activity than that of the classical surfactants was displayed by 1, 3, and 4 and an equivalent baking activity by 2. The same glycolipid classes, except 3, of different lecithin origin showed only slight differences in their baking activities, due to different fatty acid compositions. Furthermore, the glycolipid classes influenced the crumb structure significantly by improving the crumb softness and grain. Interestingly, none of the glycolipid classes showed significant antistaling effect. A direct effect on the overall rheological behavior of the dough was only found for the commercial surfactants. However, the rheological effect seen on gluten isolated from surfactant-containing dough revealed that the surfactants could be divided into two main groups, one of them directly forming and stabilizing liquid film lamellae through adsorption to interfaces and the other indirectly increasing the surface activity of the endogenous lipids in the flour. The results suggest that in wheat dough, glycolipids seem to have an impact on the dough liquor rather than on the gluten starch matrix. PMID- 19476360 TI - Comparative study on the sorption capacity of cyhalofop Acid on polymerin, ferrihydrite, and on a ferrihydrite-polymerin complex. AB - A comparative study was performed on the sorption capacity of the phenoxy acid herbicide cyhalofop on polymerin (from olive oil mill effluents), ferrihydrite, and a ferrihydrite-polymerin complex, by using a batch equilibrium method. The most efficient sorbent showed to be ferrihydrite followed by the ferrihydrite polymerin complex and polymerin. Cyhalofop acid bound to ferrihydrite by a combination of ionic and ion-dipole bonding, whereas the same herbicide bound to the ferrihydrite-polymerin complex by ionic bonding and to polymerin by hydrogen bonding. Simulated wastewaters contaminated with cyhalofop acid were completely purified by two sorption cycles on ferrihydrite and five cycles on the ferrihydrite-polymerin complex, whereas the same wastewaters maintained a constant residue even after five sorption cycles on polymerin. For the first time, the possible use of a mineral (ferrihydrite) and an organo-mineral complex (ferrihydrite-polymerin) as a filter for the control of the herbicide contamination in point sources is proposed and briefly discussed. PMID- 19476362 TI - Mass-analyzed threshold ionization (MATI) spectroscopy of atoms and molecules using VUV synchrotron radiation. AB - Mass-analyzed threshold ionization (MATI) spectroscopy using synchrotron radiation (Advanced Light Source, Lawrence Berkeley National Laboratory) has been performed for Ar, N(2), O(2), N(2)O, H(2)O, C(2)H(2), and C(6)H(6). MATI allows for a better determination of ionization energies compared to those derived from photoionization efficiency curves traditionally used in synchrotron photoionization mass spectrometry. The separation of the long-lived Rydberg state from the directly formed prompt ion, essential for a meaningful MATI spectrum, has been accomplished by employing an arrangement of ion optics coupled to unique electric field pulsing schemes. For Ar, a number of resolved bands below the ionization energy are observed, and these are ascribed to high-n,l Rydberg states prepared in the MATI scheme. The first vibrational state resolved MATI spectra of N(2) and O(2) are reported, and spectral characteristics are discussed in comparison with previously reported threshold photoelectron spectroscopic studies. Although MATI performed with synchrotron radiation is intrinsically less sensitive compared to laser-based sources, this work demonstrates that MATI spectroscopy performed with widely tunable vacuum ultraviolet (VUV) radiation is a complementary technique for studying the ionization spectroscopy of polyatomic molecules. PMID- 19476363 TI - Theoretical kinetic study of the reactions of cycloalkylperoxy radicals. AB - Reactions of alkyl radicals with oxygen are key reactions in the low-temperature oxidation of hydrocarbons, but they have not been extensively studied yet in the case of cycloalkanes. Isomerizations of cycloalkylperoxy radicals and formation of cyclic ethers are especially important. In the present work, a theoretical study of the gas-phase reactions of cyclopentylperoxy and cyclohexylperoxy radicals has been carried out by means of quantum chemical calculations at the CBS-QB3 level. Computations on cyclopentylperoxy decomposition pathways are reported here for the first time. Thermochemical data have been obtained by means of isodesmic reactions, and the contribution of hindered rotors has been explicitly taken into account. Transition state theory has been used to calculate rate constants for all the elementary reactions. Three-parameter Arrhenius expressions have been derived in the temperature range 300-1000 K. Tunneling effects have been accounted for in the case of H-atom transfers. Our results compare well with experimental data and previous calculations available in the literature. In particular, the predicted rate constants for processes involving cyclohexylperoxy radicals, which have been introduced in a reaction mechanism scheme proposed before, exhibit excellent agreement with experiments at low and intermediate temperatures. PMID- 19476364 TI - Chiral cooperativity and solvent-induced tautomerism effects in electronic circular dichroism spectra of [2.2]paracyclophane ketimines. AB - [2.2]Paracyclophanes with chiral ketimine side chains constitute a class of highly versatile and enantioselective ligands for catalytic carbon-carbon bond forming reactions. Proper matching of the side chain and [2.2]paracyclophane configurations induces chiral cooperativity, which is key to high selectivities. Here we show that the absolute configuration of both chirotropic elements may be fully resolved by CD spectroscopy and time-dependent density functional calculations. Different ketimine side chain conformations of the diastereomers perturb the planar chiral [2.2]paracyclophane chromophore. This leads to characteristic changes in the measured CD spectra and the specific rotation allowing for the simultaneous assignment of the absolute configuration of both chiral elements. Our results give rise to a simple rule relating sign and magnitude of the specific rotation and the first band of the CD spectra to the absolute configuration of both chiral elements. We infer a tautomeric equilibrium between an ortho-hydroquinone-imine and an ortho-quinone-enamine from strong solvatochromism observed in the CD spectra. PMID- 19476365 TI - Microwave spectrum of [1,1]-pyridine-Ne2. AB - We investigated the rotational spectra of six isotopologues of pyridine--Ne(2), formed by combinations of two isotopes of the nitrogen atom ((14)N and (15)N) in pyridine with two isotopes of the rare gas atoms ((20)Ne and (22)Ne), by using pulsed jet Fourier transform microwave spectroscopy. We detected the C(2v) symmetry conformer, denoted as [1,1], where the Ne atoms are located one on each side of the ring plane. The [2,0] species, with the two Ne atoms on the same side of the ring, was not observed. Two structural parameters, R and theta, that localize the rare gas atoms with respect to pyridine have been determined. The (14)N nuclear quadrupole coupling constants have been obtained for the isotopologues containing this nucleus. PMID- 19476366 TI - Direct observation of transitions between surface-dominated and bulk diffusion regimes in nanochannels. AB - The diffusion of charged proteins in liquid-filled nanometer-sized apertures with charged surfaces has been investigated with fluorescence correlation spectroscopy (FCS). Based on a two-dimensional (2D) multicomponent diffusion model, key parameters such as the number of molecules diffusing freely inside the nanochannel or interacting with the surfaces, together with the specific diffusion parameters, could be extracted. Different regimes of diffusion have been observed and described by a model, which takes into account the steric exclusion, the reversible surface adsorption of the biomolecules, and the exclusion-enrichment effect that is due to the charge of the proteins and the ionic strength of the solution. Conditions where the diffusion of proteins through nanoconfined spaces can be of the same magnitude as in the bulk were both predicted and experimentally verified. PMID- 19476367 TI - Novel metal-complexing membrane containing poly(4-vinylpyridine) for removal of Hg(II) from aqueous solution. AB - A novel poly(vinyl alcohol)/poly(4-vinylpyridine) (PVA/P(4)VP) complexing membrane for removal of Hg(II) ions from aqueous solutions represents a significant improvement over a previously reported PVA/poly(ethylenimine) (PEI) membrane. This membrane was prepared by the semi-interpenetrating polymer network technique, and its cross-linking by three different agents was studied. The best results were obtained with gaseous 1,2-dibromoethane at 140 degrees C for 1 h that gave a membrane with a swelling ratio of 0.66. The sorption reaction of Hg(II) followed a first-order rate law, and the rate-limiting step was shown to be the association of Hg(II) ions with the complexing sites of P(4)VP. Sorption experiments at pH 2.5 showed that the retention ratio could reach 100% under optimized conditions for the initial concentration of Hg(II) and mass of membrane, c(0) = 100 mg L(-1) and m(D) = 100 mg, respectively. The retention ratio was remarkably insensitive to water hardness or the presence of NaCl, suggesting possible use for the purification of real wastewaters. The retention capacity of the membrane was 450 mg g(-1) compared to 311 mg g(-1) reported for the PVA/PEI membrane. Sorption isotherms were determined at various temperatures, according to the Langmuir model, for the determination of the thermodynamical parameters. When T increased, mercury uptake at equilibrium did not change, whereas the sorption coefficient b decreased and the change in free energy DeltaG degrees decreased. This result is probably due to a large favorable entropic effect, ascribed to the displacement of protons from the protonated sites of P(4)VP while they bind with Hg(II) ions. The membrane could be regenerated by 0.5 M nitric acid with less than 3% loss of efficiency. The membrane was used for filtration experiments. The elimination ratio was 99.9% or more for filtration of Hg(II) solutions in the c(0) = 16.6-89.1 mg L(-1) range. PMID- 19476369 TI - Molecular dynamics simulations of threadlike cetyltrimethylammonium chloride micelles: effects of sodium chloride and sodium salicylate salts. AB - We use atomistic molecular dynamics simulations to probe the effects of added sodium chloride (NaCl) and sodium salicylate (NaSal) salts on the spherical-to threadlike micelle shape transition in aqueous solutions of cetyltrimethylammonium chloride (CTAC) surfactants. Long threadlike micelles are found to be unstable and break into spherical micelles at low concentrations of NaCl, but remain stable for 20 ns above a threshold value of [NaCl] approximately 3.0 M, which is about 2.5 times larger than the experimental salt concentration at which the transition between spherical and rodlike micelles occurs. The chloride counterions associate weakly on the surface of the CTAC micelles with the degree of counterion dissociation decreasing slightly with increasing [NaCl] on spherical micelles, but dropping significantly on the threadlike micelles at high [NaCl]. This effect indicates that the electrolyte ions drive the micellar shape transition by screening the electrostatic repulsions between the micellar headgroups. The aromatic salicylate counterions, on the other hand, penetrate inside the micelle with their hydrophilic groups staying in the surfactant headgroup region and the hydrophobic groups partially embedded into the hydrophobic core of the micelle. The strong association of the salicylate ions with the surfactant headgroups leads to dense packing of the surfactant molecules, which effectively reduces the surface area per surfactant, and increases intramicellar ordering of the surfactant headgroups, favoring the formation of long threadlike micelles. Simulation predictions of the geometric and electrostatic properties of the spherical and threadlike micelles are in good agreement with experiments. PMID- 19476370 TI - A microfluidic diluter based on pulse width flow modulation. AB - We demonstrate that pulse width flow modulation (PWFM) can be used to design fast, accurate, and precise multistage dilution modules for microfluidic devices. The PWFM stage unit presented here yields 10-fold dilution, but several PWFM stages can be connected in series to yield higher-order dilutions. We have combined two stages in a device thus capable of diluting up to 100-fold, and we have experimentally determined a set of rules that can be conveniently utilized to design multistage diluters. Microfabrication with resist-based molds yielded geometrical channel height variances of 7% (22.9(16) microm) with corresponding hydraulic resistance variances of approximately 20%. Pulsing frequencies, channel lengths, and flow pressures can be chosen within a wide range to establish the desired diluter properties. Finally, we illustrate the benefits of on-chip dilution in an example application where we investigate the effect of the Ca(2+) concentration on a phospholipid bilayer spreading from a membrane reservoir onto a SiO(2) surface. This is one of many possible applications where flexible concentration control is desirable. PMID- 19476372 TI - Functional group compatibility. Propargyl alcohol reduction in the presence of a vinyl iodide. AB - Vinyl iodides are stable to the reduction of propargyl alcohols to cis allylic alcohols by hydrogen over Pd/CaCO(3) in hexane. They are also stable to the reduction of propargyl alcohols to saturated alcohols by hydrogen over Crabtree's iridium catalyst in CH(2)Cl(2). PMID- 19476373 TI - Temperature and anharmonic effects on the infrared absorption spectrum from a quantum statistical approach: application to naphthalene. AB - A method is developed to calculate the finite-temperature infrared absorption spectrum of polyatomic molecules with energy levels described by a second-order Dunham expansion. The anharmonic couplings are fully incorporated in the calculation of the quantum density of states, achieved using a Wang-Landau Monte Carlo procedure, as well as in the determination of transition energies. Additional multicanonical simulations provide the microcanonical absorption intensity as a function of both the absorption wavelength and the internal energy of the molecule. The finite-temperature spectrum is finally obtained by Laplace transformation of this microcanonical histogram. The present scheme is applied to the infrared spectrum of naphthalene, for which we quantify the shifting, broadening, and third-order effects as a continuous function of temperature. The influence of anharmonicity and couplings is manifested on the nontrivial variations of these features with increasing temperature. PMID- 19476374 TI - Pincer complex-catalyzed redox coupling of alkenes with iodonium salts via presumed palladium(IV) intermediates. AB - Palladium pincer complexes directly catalyze the redox coupling reactions of functionalized alkenes and iodonium salts. The catalytic process, which is suitable for mild catalytic functionalization of allylic acetates and electron rich alkenes, probably occurs through Pd(IV) intermediates. Due to the strong metal-ligand interactions, the oxidation of phosphine and amine ligands of the pincer complexes can be avoided in the presented reactions. PMID- 19476375 TI - One-pot multicomponent coupling methods for the synthesis of diastereo- and enantioenriched (Z)-trisubstituted allylic alcohols. AB - (Z)-trisubstituted allylic alcohols are widespread structural motifs in natural products and biologically active compounds but are difficult to directly prepare. Introduced herein is a general one-pot multicomponent coupling method for the synthesis of (Z)-alpha,alpha,beta-trisubstituted allylic alcohols. (Z) trisubstituted vinylzinc reagents are formed in situ by initial hydroboration of 1-bromo-1-alkynes. Addition of dialkylzinc reagents induces a 1,2-metalate rearrangement that is followed by a boron-to-zinc transmetalation. The resulting vinylzinc reagents add to a variety of prochiral aldehydes to produce racemic (Z) trisubstituted allylic alcohols. When enantioenriched aldehyde substrates are employed, (Z)-trisubstituted allylic alcohols are isolated with high dr (>20:1 in many cases). For example, vinylation of enantioenriched benzyl-protected alpha- and beta-hydroxy propanal derivatives furnished the expected anti-Felkin addition products via chelation control. Surprisingly, silyl-protected alpha-hydroxy aldehydes also afford anti-Felkin addition products. A protocol for the catalytic asymmetric addition of (Z)-trisubstituted vinylzinc reagents to prochiral aldehydes with a (-)-MIB-based catalyst has also been developed. Several additives were investigated as inhibitors of the Lewis acidic alkylzinc halide byproducts, which promote the background reaction to form the racemate. Alpha ethyl and alpha-cyclohexyl (Z)-trisubstituted allylic alcohols can now be synthesized with excellent levels of enantioselectivity in the presence of diamine inhibitors. PMID- 19476376 TI - Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. PMID- 19476379 TI - Significantly improved sensitivity of Q-band PELDOR/DEER experiments relative to X-band is observed in measuring the intercoil distance of a leucine zipper motif peptide (GCN4-LZ). AB - Pulsed electron double resonance (PELDOR)/double electron-electron resonance (DEER) spectroscopy is a very powerful structural biology tool in which the dipolar coupling between two unpaired electron spins (site-directed nitroxide spin-labels) is measured. These measurements are typically conducted at X-band (9.4 GHz) microwave excitation using the four-pulse DEER sequence and can often require up to 12 h of signal averaging for biological samples (depending on the spin-label concentration). In this work, we present for the first time a substantial increase in DEER sensitivity obtained by collecting DEER spectra at Q band (34 GHz), when compared to X-band. The huge boost in sensitivity (factor of 13) demonstrated at Q-band represents a 169-fold decrease in data collection time, reveals a greatly improved frequency spectrum and higher-quality distance data, and significantly increases sample throughput. Thus, the availability of Q band DEER spectroscopy should have a major impact on structural biology studies using site-directed spin labeling EPR techniques. PMID- 19476382 TI - Bimetallic gold-silver nanorods produce multiple surface plasmon bands. AB - The optical properties of two-component nanorods (NRs) consisting of Au and Ag blocks were investigated. The overall optical properties of the nanorods were tailored by controlling block length. We observed two independent transverse modes in the Au and Ag blocks. Depending on the relative fraction of Au and Ag blocks, the intensity of the transverse modes varied without noticeable peak shifts. However, the strong intraparticle surface plasmon coupling between Au and Ag blocks resulted in the collective appearance of longitudinal LSP modes, including higher-order modes. This experimental observation suggests that the free electrons in Au and Ag blocks oscillate in a coherent fashion along the long axis of NRs, while there is no significant interaction in the free electron oscillation along the short axis of NRs. PMID- 19476383 TI - Morphology and secondary structure of stable beta-oligomers formed by amyloid peptide PrP(106-126). AB - The formation of nonfibrillar oligomers has been proposed to be a common element of the aggregation pathway of amyloid peptides. Here we describe the first detailed investigation of the morphology and secondary structure of stable oligomers formed by a peptide comprising residues 106-126 of the human prion protein (PrP). These oligomers have an apparent hydrodynamic radius of approximately 30 nm and are more membrane-active than monomeric or fibrillar PrP(106-126). Circular dichroism and solid state NMR data support formation of an extended beta-strand by the hydrophobic core of PrP(106-126), while negative thioflavin-T binding implies an absence of cross-beta structure in nonfibrillar oligomers. PMID- 19476380 TI - Mesoporous silica nanoparticle-based double drug delivery system for glucose responsive controlled release of insulin and cyclic AMP. AB - A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN based double-release system could lead to a new generation of self-regulated insulin-releasing devices. PMID- 19476377 TI - DNA topoisomerase I inhibitors: chemistry, biology, and interfacial inhibition. PMID- 19476384 TI - Comparative transcriptome and proteome analysis of Ha-ras and B-raf mutated mouse liver tumors. AB - Mouse liver tumors frequently harbor activating mutations in the Ha-ras protooncogene. In addition, mutations are also found in the B-raf gene leading to constitutive activation of the B-Raf kinase. In two previous studies, we have investigated by microarray analysis the effect of the mutations on the mRNA expression patterns of the respective tumors. In the present study, we analyzed proteome changes in Ha-ras and B-raf mutated liver tumors by 2-D gel electrophoretic separation of proteins followed by their identification by mass spectrometry. In total, 104 significantly altered protein spots were identified in Ha-ras mutated tumors and 111 in B-raf mutated tumors when compared to the corresponding normal liver tissue. The changes in protein expression patterns were highly correlated between Ha-ras and B-raf mutated tumors, and in the majority of the cases, both tumor types showed the respective alteration. Most of the tumor-specific changes in protein expression were reflected by similar changes in their mRNAs except for some up-regulated proteins without accompanying changes in mRNA levels. Interestingly, Ha-ras but not B-raf mutated tumors showed high levels of the phosphorylated (activated) form of the Ras/Raf/MEK effector kinase ERK which was, however, not associated with any detectable difference in the transcriptome or protein setup of the tumors. PMID- 19476385 TI - Light and molecular ions: the emergence of vacuum UV single-photon ionization in MS. AB - Thanks to recent technological advances and single-photon ionization's (SPI's) ability to detect all organics, the technique could become the long-sought universal soft ionization method. (To listen to a podcast about this feature, please go to the Analytical Chemistry Web site at pubs.acs.org/journal/ancham.). PMID- 19476386 TI - Polymer-oligopeptide composite coating for selective detection of explosives in water. AB - The selective detection of a specific target molecule in a complex environment containing potential contaminants presents a significant challenge in chemical sensor development. Utilizing phage display techniques against trinitrotoluene (TNT) and dinitrotoluene (DNT) targets, peptide receptors have previously been identified with selective binding capabilities for these molecules. For practical applications, these receptors must be immobilized onto the surface of sensor platforms at high density while maintaining their ability to bind target molecules. In this paper, a polymeric matrix composed of poly(ethylene-co glycidyl methacrylate) (PEGM) has been prepared. A high density of receptors was covalently linked through reaction of amino groups present in the receptor with epoxy groups present in the co-polymer. Using X-ray photoelectron spectroscopy (XPS) and gas-chromatography/mass spectroscopy (GC/MS), this attachment strategy is demonstrated to lead to stably bound receptors, which maintain their selective binding ability for TNT. The TNT receptor/PEGM conjugates retained 10-fold higher TNT binding ability in liquid compared to the lone PEGM surface and 3-fold higher TNT binding compared to non-specific receptor conjugates. In contrast, non-target DNT exposure yielded undetectable levels of binding. These results indicate that this polymeric construct is an effective means of facilitating selective target interaction both in an aqueous environment. Finally, real-time detection experiments were performed using a quartz crystal microbalance (QCM) as the sensing platform. Selective detection of TNT vs DNT was demonstrated using QCM crystals coated with PEGM/TNT receptor, highlighting that this receptor coating can be incorporated as a sensing element in a standard detection device for practical applications. PMID- 19476387 TI - Online magnetic bead dynamic protein-affinity selection coupled to LC-MS for the screening of pharmacologically active compounds. AB - The online, selective isolation of protein-ligand complexes using cobalt(II) coated paramagnetic affinity beads (PABs) and subsequent liquid chromatography mass spectrometry (LC-MS) determination of specifically bound ligands is described. After in-solution incubation of an analyte mixture with His-tagged target proteins, protein-analyte complexes are mixed with the Co(II)-PABs and subsequently injected into an in-house built magnetic trapping device. Bioactive ligands bound to the protein-Co(II)-PABs are retained in the magnetic field of the trapping device while inactive compounds are removed by washing with a pH 7.4 buffer. Active ligands are online eluted toward the LC-MS system using a pH shift. In the final step of the procedure, the protein-Co(II)-PABs are flushed to waste by temporarily lowering the magnetic field. The proof-of-principle is demonstrated by using commercially available Co(II)-PABs in combination with the His-tagged human estrogen-receptor ligand-binding domain. The system is characterized with a number of estrogenic ligands and nonbinding pharmaceutical compounds. The affinities of the test compounds varied from the high micromolar to the subnanomolar range. Typical detection limits are in the range from 20 to 80 nmol/L. The system is able to identify binders in mixtures of compounds, with an analysis time of 9.5 min per mixture. The standard deviation over 24 h is 9%. PMID- 19476388 TI - Determination of 13C/12C isotopic ratios of biogenic organometal(loid) compounds in complex matrixes. AB - Methylated metal(loid) compounds are formed in the environment by abiotic as well as enzymatically catalyzed transfer of a methyl group. Due to the increased mobility and toxicity in comparison to the inorganic precursors, the investigation of the formation process is of high relevance. Though the natural abundance carbon isotope ratio can give important insights toward their origin as well as the biochemical methyl transfer process, so far, these species have not been investigated by carbon isotope ratio mass spectrometry (IRMS). This is due to the analytical challenge to precisely determine the natural isotope distribution of trace amounts of metal(loid)-bound carbon in complex organic matrixes. To overcome this problem, we tested the concept of selective derivatization of nonvolatile organometal(loid)s by hydride generation (HG) followed by purge and trap (P-T) enrichment, heart-cut gas chromatography (hcGC), and subsequent analysis by GC/IRMS. Parameter optimization of HG/P-T/hcGC was conducted using online coupling to element-sensitive ICPMS (inductively coupled plasma mass spectrometry) detection. The purity of the HG/P-T/hcGC fraction was verified by GC/MS. For the model substance trimethylarsine oxide (TMAsO), an excellent agreement of the delta(13)C-value analyzed by HG/P-T/hcGC-GC/IRMS was achieved in comparison to the bulk delta(13)C-value, which shows that no significant isotope fractionation occurred during hydride generation and subsequent separation. The optimized method showed good reproducibility and a satisfying absolute detection limit of 4.5 microg TMAsO (1.2 microg(carbon)). This method was applied to the analysis of TMAsO in compost. The low delta(13)C value of this compound (-48.38 +/- 0.41 per thousand) indicates that biomethylation leads to significant carbon fractionation. HG/P-T/hcGC-GC/IRMS is a promising tool for investigation of the biomethylation process in the environment. PMID- 19476389 TI - D-amino acid detection in peptides by MALDI-TOF-TOF. AB - Detection of a D-amino acid residue in natural peptides by mass spectrometry remains a challenging task, as this post-translational modification does not induce any change in molecular mass. To our knowledge, the present article is the first report using matrix-assisted laser desorption/ionization (MALDI) for the discrimination and the quantification of peptide isomers. In this work, we used synthetic hepta- and decapeptides of biological relevance and their isomers. All L sequences and some isomers containing a D-residue in various positions were analyzed. PMID- 19476390 TI - Investigation of chemometric instrumental transfer methods for high-resolution NMR. AB - The implementation of direct standardization (DS), piecewise direct standardization (PDS), and double-window piecewise direct standardization (DWPDS) instrumental transfer techniques for high-resolution (1)H NMR spectral data was explored. The ability to transfer a multivariate calibration model developed for a "master or target" NMR instrument configuration to seven different ("secondary") NMR instrument configurations was measured. Partial least-squares (PLS) calibration of glucose, glycine, and citrate metabolite relative concentrations in model mixtures following mapping of the secondary instrumental configurations using DS, PDS, or DWPDS instrumental transfer allowed the performance of the different transfer methods to be assessed. Results from these studies suggest that DS and PDS transfer techniques produce similar improvements in the error of prediction compared to each other and provide a significant improvement over standard spectral preprocessing techniques including reference deconvolution and spectral binning. The DS instrumental transfer method produced the largest percent improvement in the predictions of concentrations for these model mixtures but, in general, required that additional transfer calibration standards be used. Limitations of the different instrumental transfer methods with respect to sample subset selection are also discussed. PMID- 19476391 TI - Integrated measurement of the mass and surface charge of discrete microparticles using a suspended microchannel resonator. AB - Measurements of the mass and surface charge of microparticles are employed in the characterization of many types of colloidal dispersions. The suspended microchannel resonator (SMR) is capable of measuring individual particle masses with femtogram resolution. Here, we employ the high sensitivity of the SMR resonance frequency to changes in particle position, relative to the cantilever tip, to determine the electrophoretic mobility of discrete particles in an applied electric field. When a sinusoidal electric field is applied to the suspended microchannel, the transient resonance frequency shift corresponding to a particle transit can be analyzed by digital signal processing to extract both the buoyant mass and electrophoretic mobility of each particle. These parameters, together with the mean particle density, can be used to compute the size, absolute mass, and surface charge of discrete microspheres, leading to a true representation of the mean and polydispersity of these quantities for a population. We have applied this technique to an aqueous suspension of two types of polystyrene microspheres, to differentiate them based on their absolute mass and their surface charge. The integrated measurement of electrophoretic mobility using the SMR is determined to be quantitative, based on comparison with commercial instruments, and exhibits favorable scaling properties that will ultimately enable measurements from mammalian cells. PMID- 19476392 TI - A digital microfluidic approach to proteomic sample processing. AB - A common characteristic for proteomic analyses is the need for extensive biochemical processing. Digital microfluidics (DMF), a technique characterized by the manipulation of discrete microdroplets (100 nL-10 microL) on an open array of electrodes, is a good match for carrying out rapid, automated solution-phase reactions. Here, we report a DMF-based method integrating several common processing steps in proteomics, including reduction, alkylation, and enzymatic digestion. Fluorogenic assays were used to quantitatively evaluate the kinetics and reproducibility of each reaction step, and MALDI-MS was used for qualitative confirmation. The method is fast, facile, and reproducible, and thus has the potential to be a useful new tool in proteomics. PMID- 19476393 TI - Total residue analysis of swabs by ion mobility spectrometry. AB - Ion mobility spectrometry (IMS) is a technique attractive for use within the pharmaceutical industry for at-line determination of residues on swabs taken from the surfaces of manufacturing equipment for the purposes of cleaning validation or verification. In this study, the development of a novel IMS method to provide a measurement of total residue present on a swab is described. The technique is based upon quantitation of charged atmospheric gas reactant ion consumption (RIC) within the instrument as a direct measure of the mass of total ionizable residue. Coupled with the conventional analysis of the active pharmaceutical ingredient within a single 2 min analysis, RIC determination provided the benefit of a single measure representative of the presence of multiple residue components or unknown components. To account for differences in response between components of a model drug product (Cymbalta) and its associated cleaning agents, a strategy was proposed to determine a "worst case" total residue test result based on RIC. A limitation of the IMS method was its incompatibility with cleaners containing a high concentration of inorganic components. The methodology provided a range from 5-50 microg per 25 cm(2) surface area and acceptable analyte recovery (50-100%). PMID- 19476394 TI - Enantioselective total synthesis of all of the known chiral cleroindicins (C-F): clarification among optical rotations and assignments. AB - Enantioselective syntheses of all of the named chiral members of the cleroindicin family (C-F) are reported. This effort demonstrates the synthetic utility of a 2,4-dihydroxybenzaldehyde as a starting material for natural product synthesis through the use sequential o-quinone methide chemistry and diastereoselective dearomatization. Natural cleroindicin F was shown to be nearly racemic, and an optically pure synthetic sample of cleroindicin F was found to racemize under slightly basic conditions. All other natural chiral cleroindicins are shown to be partially racemic. PMID- 19476395 TI - N-heterocyclic carbene-catalyzed domino ring-opening/redox amidation/cyclization reactions of formylcyclopropane 1,1-diesters: direct construction of a 6-5-6 tricyclic hydropyrido[1,2-a]indole skeleton. AB - Catalyzed by N-heterocyclic carbenes (NHCs), domino ring-opening/redox amidation/cyclization reactions of the readily available formylcyclopropane 1,1 diesters with 2-chloro-1H-indole-3-carboaldehydes were reported. This methodology provides an efficient and direct construction of a 6-5-6 tricyclic hydropyrido[1,2-a]indole skeleton, which can be potentially applied for the synthesis of several types of polycyclic indole alkaloids. PMID- 19476396 TI - Iodine-catalyzed efficient hydrophosphonylation of N-tosyl aldimines. AB - Treatment of N-tosyl aldimines with dialkyl trimethylsilyl phosphites at 0 degrees C in the presence of iodine as a catalyst afforded the corresponding sulfonamide phosphonates in excellent yields within 1.5 to 2.5 h. PMID- 19476400 TI - Is covert medication in Norwegian nursing homes still a problem? A cross sectional study. AB - BACKGROUND AND OBJECTIVE: The practice of hiding medicines in nursing home patients' food or beverages is described in only a few scientific papers. An earlier study conducted in 1999/2000 showed that covert medication was common in Norwegian nursing homes, with 11% of patients in regular nursing home units (RUs) and 17% of those in special care units for patients with dementia (SCUs) receiving at least one covert medication during the last 7 days. However, that study included few details about the medications involved. Therefore, we designed a study to obtain more detailed information about the practice of covert medication. The objectives of the study were to describe how widespread the practice is, identify the reasons for giving the medicine in disguise, determine what kinds of medicine are given in disguise, and establish who makes the decision about covert medication. METHODS: We collected data on 1,943 patients (623 in SCUs and 1,320 in RUs) in southeast Norway between October 2006 and February 2007. The information collected included what kind of drugs the patients received, what form the drugs were administered in and how the drugs were given. Patient characteristics such as age, sex, the patient's level of function in terms of activities of daily living (ADL), mental capacity and behavioural and psychological symptoms were also recorded. Ward characteristics such as the type of ward, the number of beds in the ward and the number of carers working on each shift were also documented. Descriptive statistics of the distribution of covert medication were obtained and the findings from SCUs and RUs were compared. The same approach was taken regarding information relating to who took the decision and how the practice was documented. A multilevel logistic regression analysis was performed to examine which patient and ward characteristics were associated with covert medication. RESULTS: Each patient was given on average 6.5 different medications on a regular basis every day. Nearly a quarter (23.5%) of patients who received medications had drugs mixed in food or beverages. Fourteen percent of the patients in SCUs and nearly 10% of the patients in RUs received medicine blended in food or beverages without their knowledge (covert medication). Compared with patients who were treated openly, a significantly higher proportion of patients who were treated covertly received antipsychotics (20% vs 30%, respectively; p < 0.001). In most cases, the decision to administer covert medication was made by the staff together with the physician or by the physician alone (61.4% of occasions in SCUs and 52.8% in RUs). About two-thirds of cases of covert medication had been documented to some extent in the patients' records. Low mental capacity, low ADL function and the presence of agitation and learning disability were associated with covert medication. Of the ward characteristics, only staying in SCUs was associated with covert medication. CONCLUSION: Our study presents evidence suggesting that the practice of covert medication may still be a problem in Norwegian nursing homes. The frequency of this practice has been only slightly reduced in the period 2000-7, but the practice is more frequently recorded in the patient's records and the physician is today more often involved in the decision to give medicine covertly compared with 7 years ago. PMID- 19476397 TI - Guidelines for the use of conventional and newer disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis. AB - Treatment strategies in the management of rheumatoid arthritis (RA) have significantly changed in the past decade. The early use of disease-modifying antirheumatic drugs (DMARDs) is the basis of this new treatment strategy. Because these agents alter the natural disease course of RA, early aggressive intervention results in better outcomes with respect to future structural damage and disability. The arrival of the 'biologic agents' era in rheumatology has further improved the therapeutic options in patients with RA. A significant portion of individuals with this ailment are elderly, with approximately one third of patients experiencing their first symptoms after the age of 60 years. Yet, many elderly patients with RA do not receive optimal treatment. Although the reasons for this have not been completely defined, it seems clinicians are reluctant to use DMARDs in the elderly because of uncertainty regarding their efficacy and safety in this population. The aging process is associated with important changes in drug pharmacokinetics and pharmacodynamics. It appears that the former, mainly through decreased renal clearance, is responsible for an increased incidence of adverse effects with some DMARDs. The old are also more susceptible to infection than the young, making prevention of infectious disease through vaccination of particular importance; however, healthcare professionals should be aware that some DMARDs, including biologic agents, may interfere with responses to vaccination. The available data, although limited, suggest that DMARDs, including some biologic agents, are similarly effective in the old and the young, while maintaining very good adverse effect profiles. Therefore, the elderly with RA should not be excluded from receiving optimal treatment with these medications. At the same time, clinicians must be aware of the possible increased risk of drug toxicities, recognize the need to adjust therapy to match individual patient characteristics (i.e. renal function, co-morbidities, concomitant medication use or polypharmacy), and use the lowest possible effective dosage. This review describes the special considerations to be taken into account when administering conventional (synthetic) or biologic DMARDs to elderly patients with RA. PMID- 19476399 TI - Memantine in moderately-severe-to-severe Alzheimer's disease: a postmarketing surveillance study. AB - BACKGROUND: Postmarketing surveillance studies (PMS) are an important tool for evaluating a drug's effectiveness and safety in clinical practice. To our knowledge, no PMS on memantine monotherapy for moderately-severe-to-severe Alzheimer's disease (AD) according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association criteria has been conducted to date. OBJECTIVE: The Lombardy Health Office, Italy, promoted this PMS to evaluate the effectiveness and safety of memantine in the treatment of moderately-severe-to-severe AD in clinical practice. METHODS: A total of 451 patients with moderately-severe-to-severe AD (mean age 77 +/- 7 years; 72% female), free of cholinergic medication, received memantine (standard titration to 10 mg twice daily). After 6 months of therapy, treatment effectiveness was evaluated according to two definitions of response ('no deterioration' and 'improvement'), as measured by changes in baseline scores on the Clinical Global Impression of Change, Mini-Mental State Examination, Neuropsychiatric Inventory and Activities of Daily Living scales. The safety measure was the frequency of adverse events (AEs). RESULTS: At 6-month assessment, 26.8% of subjects showed no deterioration and 3.8% showed improvement. In those showing no deterioration, response to treatment at the 3 month assessment was associated with a greater probability of a response at 6 months (adjusted odds ratio = 8.54; 95% CI 4.54, 16.05). Seventy patients (15.5%) experienced at least one AE and 39 (8.6%) discontinued treatment prematurely because of an AE. Of those who experienced an AE, 27 (38.6%) manifested behavioural and psychological symptoms of dementia. CONCLUSION: The proportion of responders to memantine treatment in this PMS was similar to that reported in a previous randomized clinical trial (26.8% vs 29%, respectively). The proportion of patients who discontinued treatment prematurely because of an AE (8.6%) was similar to that reported in two previous randomized clinical trials (10% and 12.4%). This PMS provides additional evidence that both the effectiveness and the tolerability of memantine may be transferred into real world medicine, where AD patients receiving treatment are not selected according to strict criteria. PMID- 19476402 TI - Risedronate on two consecutive days per month. AB - Risedronate, an orally administered pyridinal bisphosphonate, is effective in the treatment and prevention of postmenopausal osteoporosis. Efforts to optimize patient adherence and persistence with, and hence the effectiveness of, therapy have led to the development of a 75 mg tablet to be taken on two consecutive days each month (2CDM). After 1 year of treatment, risedronate 75 mg 2CDM was noninferior to risedronate 5 mg once daily in improving lumbar spine bone mineral density (BMD) in an ongoing (2-year) randomized, double-blind, parallel-group, multinational trial in 1229 postmenopausal women with osteoporosis. Mean percentage increases in BMD from baseline at 12 months were 3.4% and 3.6% in the 75 mg 2CDM and 5 mg once-daily groups; the upper limit of the 95% confidence interval for the treatment difference (5 mg once daily - 75 mg 2CDM; -0.19%, 0.62%) did not exceed the predefined noninferiority margin (1.5%). In general, improvements in hip BMD and reductions in bone turnover markers with the 75 mg 2CDM regimen were not significantly different from those with the 5 mg once-daily regimen; there was no significant between-group difference in the incidence of new vertebral fractures at 12 months. The tolerability profile (including the incidence of upper gastrointestinal tract adverse events) of risedronate 75 mg 2CDM in postmenopausal women with osteoporosis was similar to that of risedronate 5 mg once daily. PMID- 19476401 TI - Polypharmacy among disabled Taiwanese elderly: a longitudinal observational study. AB - BACKGROUND AND OBJECTIVE: It is not known whether the correlates of polypharmacy among disabled elderly are similar to those for older adults in general. Furthermore, data on polypharmacy in the Taiwanese population are limited. Therefore, this study was conducted to determine the prevalence and correlates of polypharmacy among disabled Taiwanese elderly (aged >or=65 years). METHODS: This was a longitudinal observational study conducted on information obtained between July 2001 and June 2002. Study participants consisted of nationally representative samples of 11,788 disabled Taiwanese elderly from the ANLTCNT (Assessment of National Long-Term Care Need in Taiwan) study. Polypharmacy and major polypharmacy were defined as prescription of >or=5 and >or=10 medications, respectively, on the day of maximum numbers of prescriptions of the study year. Subject characteristics were derived from the ANLTCNT study survey data. Healthcare-related characteristics, including medication prescriptions, were obtained from the National Health Insurance (NHI) claims data. Multivariate logistic regression was performed for statistical analysis. RESULTS: One-fifth (21.5%) of the sample were aged >or=85 years, and 58% were female. The prevalence of polypharmacy and major polypharmacy among disabled Taiwanese elderly was 81% and 38%, respectively. Nearly one-third (32.5%) of disabled Taiwanese elderly were exposed to polypharmacy for >or=181 days in 1 year. Compared with those with a low tendency for visiting multiple providers, those with intermediate tendency (odds ratio [OR] 3.61; 95% CI 3.11, 4.18) and those with high tendency (OR 10.24; 95% CI 8.56, 12.24) were more likely to be exposed to polypharmacy. Other significant correlates of polypharmacy in the multivariate logistic regression model included age <85 years, living in urban areas, higher number of chronic conditions, poorer physical functioning, preference for visiting independent clinics and not being institutionalized. CONCLUSION: The prevalence of polypharmacy was extremely high among disabled Taiwanese elderly. Visiting multiple healthcare providers was one of the strongest correlates. Policies that encourage the disabled elderly to establish primary care relationships and that promote geriatric care models may decrease the prevalence of polypharmacy and associated adverse outcomes in this group. PMID- 19476398 TI - Off-label use of bevacizumab for the treatment of age-related macular degeneration: what is the evidence? AB - There is an active and controversial debate about the role of intravitreal bevacizumab versus approved drugs in the treatment of neovascular age-related macular degeneration (AMD). Because bevacizumab was available prior to the launch of ranibizumab, off-label use of the former became widespread and the cancer drug bevacizumab is the most commonly used medication in ophthalmology nowadays. This review considers every publication identified in MEDLINE using the keywords 'bevacizumab' and 'Avastin' between 1 June 2005 and 31 July 2008. The search identified 511 papers that were evaluated. In 33 studies, there was consistent and clear evidence for the efficacy of bevacizumab in neovascular AMD. However, the highest grade studies (three prospective, randomized, controlled trials) did not attain better than grade 2b level of evidence, and objective evaluation of the benefit of bevacizumab relative to representative controls was therefore not possible. Certainly, the available evidence is inferior to that obtained from the approval studies of ranibizumab and this should influence treatment selection and guidance of patients. These considerations indicate that important quality criteria need to be included in future studies to ensure more meaningful conclusions can be drawn. These include clearly defined inclusion criteria, information about the recruitment procedure (including data on withdrawals, excluded patients, concealed treatment allocation, use of intention-to-treat analyses and blinded assessment procedures). Although preclinical studies have almost exclusively found bevacizumab to be safe, the design utilized in clinical case series cannot rule out a possible increase in adverse events, which already show a high spontaneous incidence in elderly AMD patients. The superior evidence level for ranibizumab and the limited safety data for bevacizumab must be taken into consideration when evaluating the costs that a healthcare system is willing to spend. However, the superior grade of evidence for ranibizumab should not be confused with the (still missing) evidence for superior efficacy. The results of ongoing randomized, controlled, comparative trials will provide further data on the efficacy and cost effectiveness of bevacizumab and ranibizumab in the treatment of AMD. In the meantime, patients should be informed about the alternatives, the price differences and the restricted liability issue when off label use of bevacizumab is offered. PMID- 19476404 TI - Distinct phosphatase activity profiles in two strains of Trypanosoma cruzi. AB - Phosphorylation of parasite proteins plays a key role in the process of cell invasion by Trypanosoma cruzi, the etiologic agent of Chagas' disease. In this sense, characterization of parasite kinases and phosphatases could open new possibilities for the rational design of chemotherapeutic agents for the treatment of Chagas' disease. In this work, we analyzed phosphatase activities in T. cruzi homogenates from 2 strains belonging to different lineages and with different resistance to oxidative stress. Tulahuen 2 cells (Lineage I) showed higher phosphatase activities and specificity constants when compared to the Y strain (Lineage II). Tulahuen 2 had an optimum phosphatase activity at pH 4.0 and the Y strain at pH 7.0. In both cases, neutral-basic, but not acid, phosphatase activities were increased in the presence of Mg2+. Although calcium had an inhibitory effect at a pH of 7.0 and 8.0 in the Y strain, this inhibition was restricted to pH 8.0 in the other strain. Different substrates and acid phosphotyrosine and alkaline phosphatase inhibitors exhibited distinct effects on the phosphatase activity of both strains. Our results provide a better understanding of T. cruzi phosphatases and reinforce the notion of heterogeneity among T. cruzi populations. PMID- 19476405 TI - Pollen challenge study of a phototherapy device for reducing the symptoms of hay fever. AB - OBJECTIVE: The objective was to investigate the effect of intranasal phototherapy delivered by a phototherapy device (allergy reliever SN-206) on symptoms of hay fever (seasonal rhinitis) due to grass pollen in adults. This registered class IIA medical device had been on sale for 15 months with no adverse effects reported but there had been no assessment of efficacy. Previous research had indicated that phototherapy could alleviate symptoms of allergic rhinitis but no double-blind, placebo-controlled trails had been done. RESEARCH DESIGN AND METHODS: The trial is a double-blind, placebo-controlled grass pollen challenge conducted out of the pollen season, on 101 adult male and female hay fever sufferers. Subjects were assigned to placebo or active groups by stratified random sampling using responses to a baseline questionnaire. All subjects used active or placebo devices three times a day for 14 days before pollen challenge. Subjects were monitored for 2.5 h after challenge. MAIN OUTCOME MEASURES: Primary outcome measures were observed severity scores for sneezing, running eyes, running nose, and the amount of eosinophil cationic proteins (ECP) in nasal secretions. Secondary outcome measures were symptom scores by subject report (itching eyes, itching nose, itching throat, itching mouth/palate), and nasal peak inspiratory flow (PIFn) and peak expiratory flow (PEFn). RESULTS: Significant reductions in severity of symptom scores were found for sneezing, running nose, running eyes and itchy mouth/palate (p < or = 0.05). No significant differences were found in the results for itchy eyes, itchy nose, itchy throat, ECPs, PIFn and PEFn. No adverse events occurred. CONCLUSIONS: The results show that the device significantly reduced some hay fever symptoms. The study would have been improved if compliance was monitored electronically and if nasal congestion was monitored by report. The mode of action is unclear. The study does not consider long-term implications of the therapy. PMID- 19476406 TI - Three-month, randomized, parallel-group comparison of brimonidine-timolol versus dorzolamide-timolol fixed-combination therapy. AB - OBJECTIVE: Fixed combinations of 0.2% brimonidine-0.5% timolol and 2% dorzolamide 0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine-timolol compared with dorzolamide-timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension. STUDY DESIGN AND METHODS: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine-timolol BID or dorzolamide-timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79). CLINICAL TRIAL REGISTRATION: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov. MAIN OUTCOME MEASURES: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire. RESULTS: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide-timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine-timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide-timolol (p = 0.213). Patients on brimonidine timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide-timolol. CONCLUSIONS: Fixed combination brimonidine-timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide-timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine-timolol received higher ratings of ocular comfort than dorzolamide-timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine-timolol and dorzolamide-timolol during long-term treatment. PMID- 19476407 TI - Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability. AB - BACKGROUND: Policy makers around the world are currently considering the creation of a regulatory pathway for follow-on biologics (FOB), which will have to account for the substantial technical challenges associated with FOB development. These challenges will likely involve more complexity than comparability assessments of process changes made by the same manufacturer. The history of industry-regulator comparability discussions helps explain why the same degree of testing and flexibility now applied to change-control within a manufacturer's own process, at this time, cannot be extrapolated to the observed and possibly unknown differences between two manufacturing processes that are independently developed by different (non-collaborating) parties. OBJECTIVES: This commentary provides recommendations on the technical aspects that should be considered in the creation of an approval pathway for FOB products. CONCLUSIONS: In the authors' view, analytical methodology in its current state cannot alone provide full assurance that the FOB is sufficiently similar to the innovator product. Moreover, the FOB manufacturer will not have access to the extensive knowledge accumulated by the innovator manufacturer from early development through marketing. Thus, extensive clinical evaluation will likely be necessary to provide assurance that the FOB is safe and efficacious. If such testing demonstrates the FOB is safe and efficacious per existing regulatory standards, the product should receive marketing approval as a 'similar' product. Since 'similarity' is a fundamentally different determination than establishing interchangeability between the two products, an interchangeability determination must be based on additional testing and market experience to ensure patient safety. Post-marketing surveillance of the FOB should be conducted to ensure that the approved molecule has similar clinical safety and efficacy as the innovator product, prior to any consideration of interchangeability. PMID- 19476408 TI - Markers of oxidative status in a clinical model of oxidative assault: a pilot study in human blood following doxorubicin administration. AB - We used doxorubicin-based chemotherapy as a clinical model for oxidative assault. Study recruited 23 breast cancer patients and collected blood samples before (T0), at 1 (T1) and 24 hours (T24) after treatment administration. Measurements included protein carbonyl content (PPCC), malondialdehyde (MDA), and alpha- and gamma-tocopherols in plasma and total glutathione content in erythrocytes (erGSHt). In all subjects, PPCC and MDA levels did not change. erGSHt levels increased at T24 by 8% (p=0.03). Levels of alpha, gamma, and total tocopherols progressively decreased by 7%-15% (p <0.05). In subjects with low erGSHt levels (below median), PPCC mean levels progressively increased from 0.35 (T0) to 0.56 (T1) and 0.72 nmol carbonyl/mg protein (T24) (p =0.2). These results indicate that (1) plasma MDA is not a sensitive biomarker in humans; (2) PPCC potentially may be used, if antioxidant reserves are taken into account; (3) antioxidant reserves play an important role in the reaction to oxidative stress. PMID- 19476409 TI - Biochemical and proteomic effects in Procambarus clarkii after chlorpyrifos or carbaryl exposure under sublethal conditions. AB - In vivo effects of two sublethal doses of chlorpyrifos and carbaryl were studied in Procambarus clarkii after 2 and 7 days of exposure, and after pesticide removal. Chlorpyrifos inhibited carboxylesterase activity in a concentration dependent manner, but acetylcholinesterase was less sensitive. Compared with chlorpyrifos, carbaryl had a less marked effect on esterase activity. The effects of selected pesticides on biotransformation or oxidative stress biomarkers were contradictory. Chlorpyrifos lowered ethoxyresorufin-O-deethylase (EROD), catalase and oxidized glutathione (GSSG) levels but raised glutathione-S-transferase activity, while carbaryl raised EROD, catalase and glutathione-S-transferase, but lowered glutathione peroxidase and reduced glutathione (GSH) levels. The effects on protein expression patterns depending on pesticide type and the tissue used for analysis were studied in parallel by 2-DE. In gill and nervous tissue about 2000 spots (pI 4-7) were resolved, with quite different expression patterns. Chlorpyrifos altered 72 proteins, mostly in nervous tissue, and carbaryl 35, distributed evenly between organs. Several specific spots were selected as specific protein expression signatures for chlorpyrifos or carbaryl exposure in gills and nervous tissue, respectively. PMID- 19476410 TI - Analysis of myosmine, cotinine and nicotine in human toenail, plasma and saliva. AB - Myosmine is a minor tobacco alkaloid with widespread occurrence in the human diet. Myosmine is genotoxic in human cells and is readily nitrosated and peroxidated yielding reactive intermediates with carcinogenic potential. For biomonitoring of short-term and long-term exposure, analytical methods were established for determination of myosmine together with nicotine and cotinine in plasma, saliva and toenail by gas chromatography-mass spectrometry (GC/MS). Validation of the method with samples of 14 smokers and 10 non-smokers showed smoking-dependent differences of myosmine in toenails (66 +/- 56 vs 21 +/- 15 ng g(-1), p <0.01) as well as saliva (2.54 +/- 2.68 vs 0.73 +/- 0.65 ng ml(-1), p <0.01). However, these differences were much smaller than those with nicotine (1971 +/- 818 vs 132 +/- 82 ng g(-1), p <0.0001) and cotinine (1237 +/- 818 vs <35 ng g(-1)) in toenail and those of cotinine (97.43 +/- 84.54 vs 1.85 +/- 4.50 ng ml(-1), p <0.0001) in saliva. These results were confirmed in plasma samples from 84 patients undergoing gastro-oesophageal endoscopy. Differences between 25 smokers and 59 non-smokers are again much lower for myosmine (0.30 +/- 0.35 vs 0.16 +/- 0.18 ng ml(-1), p <0.05) than for cotinine (54.67 +/- 29.63 vs 0.61 +/- 1.82 ng ml(-1), p <0.0001). In conclusion, sources other than tobacco contribute considerably to the human body burden of myosmine. PMID- 19476411 TI - Assessment of the total effective xenoestrogen burden in extracts of human placentas. AB - We have standardized a method to assess the total effective xenoestrogen burden (TEXB) in human placentas by the extraction and separation by high-performance liquid chromatography of two fractions containing lipophilic xenoestrogens (alpha) and endogenous hormones (beta), followed by assessing their estrogenicity in MCF-7 breast cancer cell-based E-Screen and Yeast Estrogen Screen (YES) bioassays. The means of TEXB alpha concentrations (in estradiol equivalent (Eeq) units) were 1.32 and 0.77 Eeq pM g(-1) placenta in the E-Screen and YES, respectively; TEXB beta concentrations were 6.97 and 11.56 Eeq pM g(-1) placenta, respectively. The interclass correlation coefficient was low and a fair level of agreement was observed after kappa test correction. According to the E-Screen and YES, TEXB alpha was > or = LOD in 70.0 and 55.0% of the placentas and 92.5 and 82.5% in beta, respectively. Although both bioassays can be recommended for assessing TEXB, there is greater experience with the use of the E-Screen for estrogenic assessment after extensive extraction of complex human matrices. PMID- 19476412 TI - Diploidy, population structure, and the evolution of recombination. AB - In diploids, sex affects genetic variation through segregation and recombination. Several recent models on the advantage of recombination have focused on the effect of interaction between selection and drift in finite or structured populations; however, these models considered haploid organisms. In this article, I present a three-locus model of the evolution of recombination in structured diploid populations, including dominance and epistatic effects among alleles. This model shows that dominance generates a selective force against recombination due to the fact that recombination reduces correlations in homozygosity that are generated by population structure. This result is confirmed by multilocus simulations (representing deleterious mutations occurring over a whole genome), showing that when mutations are sufficiently recessive, the population evolves to zero recombination. In the presence of epistasis, the same effect of recombination on correlations in homozygosity generates an advantage for recombination under negative dominance by dominance epistasis (e(d x d)). Additive by additive epistasis (e(a x a)) favors recombination when it is negative and sufficiently weak, while additive by dominance epistasis has less effect. Some of these effects, however, are reversed when the deleterious mutation rate U is sufficiently high: in that case, strongly negative (e(a x a)) can favor recombination, while negative (e(d x d)) disfavors it. Interpretation of these results is given. PMID- 19476414 TI - Protein disulfide isomerase: a critical evaluation of its function in disulfide bond formation. AB - Disulfide bond formation is probably involved in the biogenesis of approximately one third of human proteins. A central player in this essential process is protein disulfide isomerase or PDI. PDI was the first protein-folding catalyst reported. However, despite more than four decades of study, we still do not understand much about its physiological mechanisms of action. This review examines the published literature with a critical eye. This review aims to (a) provide background on the chemistry of disulfide bond formation and rearrangement, including the concept of reduction potential, before examining the structure of PDI; (b) detail the thiol-disulfide exchange reactions that are catalyzed by PDI in vitro, including a critical examination of the assays used to determine them; (c) examine oxidation and reduction of PDI in vivo, including not only the role of ERo1 but also an extensive assessment of the role of glutathione, as well as other systems, such as peroxide, dehydroascorbate, and a discussion of vitamin K-based systems; (d) consider the in vivo reactions of PDI and the determination and implications of the redox state of PDI in vivo; and (e) discuss other human and yeast PDI-family members. PMID- 19476415 TI - Reduction in mortality associated with statin therapy in patients with severe sepsis. AB - STUDY OBJECTIVE: To evaluate the effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on mortality in patients with severe sepsis. DESIGN: Retrospective cohort study. SETTING: Intensive care unit (ICU) of an academic medical center. PATIENTS: One hundred eighty-eight patients aged 40 years or older with a diagnosis of severe sepsis and an ICU stay between January 1, 2005, and December 31, 2006. MEASUREMENTS AND MAIN RESULTS: Patient demographic data, statin use, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at the time of sepsis diagnosis were collected from the patient database. We used a multivariable logistic regression model to evaluate the association between statin use and in-hospital all-cause mortality after controlling for age, sex, and severity of illness. Of the 188 patients who met our inclusion criteria, 60 (32%) had statin exposure. Patients receiving statins were similar in age, sex, and APACHE II scores to those not receiving statins. In the univariable comparison, the statin group had a 35% relative reduction in mortality compared with the nonstatin group (mortality rate 31.7% vs 48.4%, p=0.040). Most of the mortality reduction attributed to statins occurred in patients with APACHE II scores higher than 24 (mortality rate 32.3% vs 57.5%, p=0.031), with a minimal mortality difference in patients with APACHE II scores of 24 or lower (31% vs 36.4%, p=0.810). In the multivariable regression model, statin use had a protective effect (odds ratio [OR] 0.42, 95% confidence interval [CI] 0.21-0.84, p=0.014), whereas increasing age (OR 1.03, 95% CI 1.01-1.06, p=0.013) and higher APACHE II score (OR 1.11, 95% CI 1.05-1.18, p=0.001) were associated with increased mortality. CONCLUSION: The use of statins was associated with a protective effect in patients with severe sepsis, as demonstrated by a significant reduction in mortality compared with patients not receiving statins. PMID- 19476416 TI - Weight-based dosing of enoxaparin in obese patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE initiative. AB - STUDY OBJECTIVE: To evaluate how enoxaparin is dosed in contemporary clinical practice as a function of patients' total body weight (TBW) and body mass index (BMI), and to determine any association between dose and major bleeding. DESIGN: Retrospective cohort study. DATA SOURCE: The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology-American Heart Association Guidelines (CRUSADE) national quality improvement initiative database. PATIENTS: A total of 19,061 patients enrolled in the CRUSADE initiative between January 1, 2004, and March 31, 2006, who received enoxaparin for the initial treatment of non-ST segment elevation acute coronary syndromes. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data, enoxaparin doses, and frequency of major bleeding unrelated to coronary artery bypass graft (CABG) surgery were compared among patient groups stratified by TBW(< or = 100, 101-120, 121-150, and > 150 kg). Adjusted odds ratios (OR) of major bleeding unrelated to CABG surgery were calculated with each dose increase of 0.25 mg/kg stratified by BMI (< 18.5, 18.5 24.9, 25.0-29.9, and > or = 30 kg/m(2)), as well as for patients receiving a reduced dose (< 0.95 mg/kg) compared with those receiving a recommended dose (0.95-1.05 mg/kg), stratified by TBW. An inverse association was noted between enoxaparin dose and patient weight. Median initial doses were 1 mg/kg in those weighing 100 kg or less, 0.96 mg/kg in those 101-120 kg, 0.92 mg/kg in those 121 150 kg, and 0.65 mg/kg in those weighing more than 150 kg (p<0.0001 for < or = 100 kg vs > 150 kg). Up to 80% of patients weighing more than 150 kg received an initial enoxaparin dose below the recommended dose. In contrast to patients with normal body weight, those weighing more than 150 kg who received a recommended dose of enoxaparin had a higher bleeding risk relative to those who received a lower dose (adjusted OR 2.42, 95% confidence interval 0.70-8.37). CONCLUSION: Clinicians tend to use reduced weight-based doses of enoxaparin in overweight and obese patients. Although data are limited, use of the recommended enoxaparin dose of 1 mg/kg is associated with a higher bleeding risk in those weighing more than 150 kg. Thus, further study of enoxaparin dosing in very obese patients with non ST-segment elevation acute coronary syndromes is warranted. PMID- 19476417 TI - Effects of hawthorn on the progression of heart failure in a rat model of aortic constriction. AB - STUDY OBJECTIVE: To determine the effects of hawthorn (Crataegus oxycantha) on left ventricular remodeling and function in pressure overload-induced heart failure in an animal model. DESIGN: Randomized, parallel, dose-ranging animal study. SETTING: University research facility. ANIMALS: Seventy-four male Sprague Dawley rats; 44 were included in the final analysis. INTERVENTION: Rats underwent a sham operation or aortic constriction. Rats subjected to the sham operation were treated with vehicle (10% agar-agar), and those subjected to aortic constriction were treated with vehicle or hawthorn (C. oxycantha special extract WS 1442) 1.3, 13, or 130 mg/kg for 5 months. MEASUREMENTS AND MAIN RESULTS: Rats and their hearts were weighed, and echocardiographic measurements were performed at baseline and at 2, 3, 4, and 5 months after aortic constriction. Protein expression for markers of fibrosis and for atrial natriuretic factor was also measured. Aortic constriction increased the left ventricular:body weight ratio by 53% in vehicle-treated rats; Hawthorn treatment did not significantly affect the aortic constriction-induced increase in this ratio. Left ventricular volumes and dimensions at systole and diastole significantly increased 5 months after aortic constriction compared with baseline in rats given vehicle (> 20% increase, p<0.05) but not in those given hawthorn 130 mg/kg (< 10% increase). After aortic constriction, the velocity of circumferential shortening significantly decreased in the vehicle group but not in the medium- or high-dose groups. In the aortic constriction-vehicle group, the induced increases in messenger RNA expression for atrial natriuretic factor (approximately 1000%) and fibronectin (approximately 80%) were significantly attenuated by high-dose hawthorn treatment by approximately 80% and 50%, respectively. CONCLUSION: Hawthorn treatment exhibited modest beneficial effects on cardiac remodeling and function during long-term, pressure overload-induced heart failure in rats. PMID- 19476418 TI - Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for dosing antimicrobials. AB - STUDY OBJECTIVES: To determine the concordance between the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations for glomerular filtration rate (GFR) estimation, the impact of using each equation on antimicrobial dosing, the difference in estimated GFR in patients with acute kidney disease (AKD) versus chronic kidney disease (CKD), and the correlation between the MDRD, Cockcroft-Gault equation, and expert medical opinion for estimating GFR in patients with AKD. DESIGN: Retrospective cohort study. SETTING: A 689-bed academic medical center. PATIENTS: A total of 372 adults hospitalized with either AKD or CKD between January 1, 2007, and May 31, 2007, and who received at least one antimicrobial drug; patients with stage 1 or 2 CKD or those receiving dialysis were excluded. MEASUREMENTS AND MAIN RESULTS: Data were collected from electronic medical records on patient characteristics, laboratory values, antimicrobial drugs requiring dosage adjustment due to renal dysfunction, and estimated GFRs provided by the laboratory (MDRD estimation). In addition, estimated GFRs were calculated using the Cockcroft-Gault equation. For patients with AKD, a third GFR was estimated by a nephrologist. For all patients, the MDRD GFR was significantly higher than the Cockcroft-Gault GFR (p<0.001). Level of concordance for the need for dosage adjustment based on the two equations was moderate (kappa coefficient 0.57, 95% confidence interval 0.5-0.63); 99.1% of patients with discordant dose recommendations would receive a higher dose if the MDRD GFR was used. In the AKD versus CKD groups, mean MDRD GFR was significantly higher than the Cockcroft-Gault GFR in both groups (p<0.0001), but the difference was significantly greater in the CKD group (p<0.0001). In patients with AKD, the GFR estimated by expert opinion was greater than that estimated by the Cockcroft Gault equation (p=0.04), but was similar to the MDRD equation (p=0.07). CONCLUSION: The estimated GFR obtained with the MDRD equation was consistently higher than that from the Cockcroft-Gault equation in patients with AKD or CKD. In patients with AKD, the MDRD GFR more closely correlated with expert opinion than the Cockcroft-Gault, suggesting that the MDRD method may be applicable to this patient population. Moderate concordance between the two equations for the need for antimicrobial dosage adjustment due to renal dysfunction was found, but the specific dosage change was different for approximately 40% of patients, with 99% receiving higher doses when the MDRD GFR is used. These dosing differences may be significant, depending on drug safety profile, type of infection, and causative pathogen. PMID- 19476419 TI - Attention-deficit-hyperactivity disorder: an update. AB - Attention-deficit-hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that impairs social, academic, and occupational functioning in children, adolescents, and adults. In patients with ADHD, neurobiologic research has shown a lack of connectivity in key brain regions, inhibitory control deficits, delayed brain maturation, and noradrenergic and dopaminergic dysfunction in multiple brain regions. The prevalence of this disorder in the United States is 6-9% in youth (i.e., children and adolescents) and 3-5% in adults. Prevalence rates for youth are similar worldwide. Children with ADHD are at greater risk than children without ADHD for substance abuse and delinquency whether or not they receive drug therapy; however, early treatment with psychoeducation as well as drug therapy and/or behavioral intervention may decrease negative outcomes of ADHD, including the rate of conduct disorder and adult antisocial personality disorder. Drug therapy is effective for all age groups, even preschoolers, and for late-onset ADHD in adults. Stimulants, such as methylphenidate and amphetamine, are the most effective therapy and have a good safety profile; although recent concerns of sudden unexplained death, psychiatric adverse effects, and growth effects have prompted the introduction of other therapies. Atomoxetine, a nonstimulant, has no abuse potential, causes less insomnia than stimulants, and poses minimal risk of growth effects. Other drug options include clonidine and guanfacine, but both can cause bradycardia and sedation. Polyunsaturated fatty acids (fish oil), acetyl-L carnitine, and iron supplements (for youth with low ferritin levels) show promise in improving ADHD symptoms. As long-term studies show that at least 50% of youth are nonadherent with their drug therapy as prescribed over a 1-year period, long acting formulations (administered once/day) may improve adherence. Comorbid conditions are common in patients with ADHD, but this patient population can be treated effectively with individualized treatment regimens of stimulants, atomoxetine, or bupropion, along with close monitoring. PMID- 19476420 TI - Optimizing pediatric dosing: a developmental pharmacologic approach. AB - Many physiologic differences between children and adults can result in age related differences in pharmacokinetics. Understanding the effects of age on bioavailability, volume of distribution, protein binding, hepatic metabolic isoenzymes, and renal elimination can provide insight into optimizing doses for pediatric patients. We performed a search of English-language literature using the MEDLINE database regarding age and pharmacokinetics (1979-July 2008). We then evaluated the literature with an emphasis on drugs with one primary elimination pathway, such as renal clearance or a pathway involving a single metabolic isoenzyme. Our mechanistic-based analysis revealed that children need weight corrected doses that are substantially higher than adult doses for drugs that are metabolically eliminated solely by the specific cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2C9, and CYP3A4. In contrast, weight-corrected doses for drugs eliminated by renal excretion or metabolism involving CYP2C19, CYP2D6, N acetyltransferase 2, or uridine diphosphate glucuronosyltransferases are similar in children and adults. In children, bioavailability of drugs with high first pass metabolism is decreased for drugs metabolized by CYP1A2, CYP2C9, and CYP3A4. Limited data suggest that by age 5 years, bioavailability of drugs affected by efflux transporters should be equivalent to that of adults. Using a pharmacokinetics-based approach, rational predictions can be made for the effects of age on drugs that undergo similar pathways of elimination, even when specific pharmacokinetic data are limited or unavailable. PMID- 19476421 TI - Vitamin D and cardiovascular disease. AB - The hormonal derivative of vitamin D, 1,25-dihydroxyvitamin D (1,25[OH](2)D) or calcitriol, has been implicated in many physiologic processes beyond calcium and phosphorus homeostasis, and likely plays a role in several chronic disease states, in particular, cardiovascular disease. Experimental data suggest that 1,25(OH)(2)D affects cardiac muscle directly, controls parathyroid hormone secretion, regulates the renin-angiotensin-aldosterone system, and modulates the immune system. Because of these biologic effects, vitamin D deficiency has been associated with hypertension, several types of vascular diseases, and heart failure. We conducted a MEDLINE search of the English-language literature (1950 2008) to identify studies that examined these relationships; additional citations were obtained from the articles retrieved from the literature search. Treatment with vitamin D lowered blood pressure in patients with hypertension and modified the cytokine profile in patients with heart failure. Measurement of serum 25 hydroxyvitamin D concentration usually provides the best assessment of an individual's vitamin D status. Serum levels below 20 ng/ml represent vitamin D deficiency, and levels above 30 ng/ml are considered optimal. Although the observational data linking vitamin D status to cardiovascular disease appear robust, vitamin D supplementation is not recommended as routine treatment for heart disease until definitive prospective, randomized trials can be carried out to assess its effects. However, such supplementation is often appropriate for other reasons and may be beneficial to cardiovascular health in certain patients. PMID- 19476422 TI - Treatment of acute promyelocytic leukemia during pregnancy. AB - Management of the pregnant patient with acute promyelocytic leukemia (APL) is a challenge. Immediate treatment of APL is critical, as it is an oncologic emergency, with a high risk of morbidity and mortality associated with disseminated intravascular coagulation. However, administration of chemotherapy and differentiating agents in pregnancy is controversial because of potential teratogenic effects. In addition, complications associated with APL, including retinoic acid syndrome, add to the complexity of management. To better understand how to manage this complex patient care situation, we searched the PubMed database (January 1972-May 2008) for English-language articles about maternal and fetal outcomes resulting from APL treatment during pregnancy. A total of 42 cases from 35 articles were identified: 12 first-trimester, 21 second-trimester, and 9 third-trimester cases. The most commonly administered agents were all-trans retinoic acid (ATRA), anthracyclines, and antimetabolites. Complete remission was reported in 35 (83%) of 42 patients. Administration of ATRA or chemotherapy in the first trimester was associated with an increased risk of fetal malformations and spontaneous abortion, whereas administration in the second and third trimesters was associated with relatively favorable fetal outcomes. The overall treatment of the pregnant patient with APL should include a discussion about pregnancy termination, especially if APL is diagnosed in the first trimester. If the pregnancy is to continue, then the appropriate chemotherapy regimen needs to be determined. Frequent fetal monitoring, along with aggressive management of potential APL-related complications, is necessary to allow for optimal maternal and fetal outcomes. PMID- 19476423 TI - Management of atypical antipsychotic drug-induced weight gain: focus on metformin. AB - Many patients taking atypical antipsychotic drugs will experience weight gain. Evidence suggests that long-term treatment with these agents decreases glucose effectiveness, alters satiety signals, creates hormonal resistance to satiety control, and may have a direct effect on hypothalamic appetite centers. The serotonin(2c-) and histamine(1)-receptor antagonism of atypical antipsychotics may also lead to weight gain. Several nonpharmacologic and pharmacologic methods have been used to address this adverse effect, with varying success. Metformin is an antidiabetic drug that has been shown to cause weight loss in patients with diabetes mellitus, as well as in some individuals without diabetes. To evaluate whether metformin can decrease weight gain induced by atypical antipsychotics in patients without diabetes, we conducted a literature search using the MEDLINE database (1970-October 2008) and clinicaltrials.gov Web site for relevant trials. Overall, 14 articles were identified for inclusion; review articles, case reports, and open-label studies were excluded. Thus, eight double-blind, placebo controlled studies were reviewed; both pediatric and adult trials were included. Metformin has several advantages, including ease of use and a favorable safety profile. Although lactic acidosis was not reported in any of the studies reviewed, this potentially rare but severe adverse effect must be considered when prescribing this agent. Limited data suggest that metformin may attenuate weight gain in both adult and adolescent patients taking atypical antipsychotics. However, most of the trials included foreign populations, were only 12-16 weeks in duration, and the dosage of metformin may not have been adequately titrated. Although the study results do not provide clear substantial evidence that metformin, as an adjuvant to atypical antipsychotic use, will decrease weight gain and improve metabolic effects, they are encouraging. Additional studies of longer duration that include behavioral therapy and special diets should be conducted in patients from the United States. Currently, the drug is being used as a secondary or tertiary intervention, and its use may be considered in patients with a personal and/or family history of obesity or metabolic dysfunction, and in subjects who have rapid weight gain early in antipsychotic treatment. PMID- 19476424 TI - An antimicrobial stewardship program with a focus on reducing fluoroquinolone overuse. AB - The fluoroquinolones have become the leading class of antimicrobial agents prescribed to adults in the United States. Resistance of key pathogens to fluoroquinolones has developed rapidly in parallel with increased prescribing of these drugs. We describe our pharmacist-led antimicrobial stewardship program that focused on reducing inappropriate prescribing of fluoroquinolones, with the goals of limiting the development of resistance and improving patient outcomes. Core strategies were regular monitoring and reporting of resistance trends observed on institutional antibiograms, performing drug audits and related studies with intervention and feedback to prescribers, implementing an automatic parenteral-to-oral conversion program, establishing and implementing a beta lactam-based institutional guideline for empiric therapy, and educating prescribers. This successful program reduced empiric prescribing of fluoroquinolones by 30%, improved susceptibility for all antipseudomonal agents against Pseudomonas aeruginosa overall by 10%, and decreased mortality associated with P. aeruginosa infections by 2-fold. Our stewardship program clearly demonstrated that pharmacists can take on leadership roles to positively change antimicrobial prescribing at the institutional level and improve patient outcomes. PMID- 19476425 TI - Interaction between gemfibrozil and warfarin: case report and review of the literature. AB - Possible procoagulant effects can occur when lipid-lowering fibric acid derivatives, such as gemfibrozil and fenofibrate, are taken concomitantly with warfarin. Although there are several detailed reports of fenofibrate potentiating the anticoagulant effects of warfarin, few case reports have been published regarding an interaction between gemfibrozil and warfarin. We describe a 62-year old man who was taking warfarin for paroxysmal atrial fibrillation and came to the anticoagulation clinic for a routine follow-up. For 9 months, the patient's international normalized ratio (INR) had been stable (target range 2.0-3.0) with warfarin 45 mg/week. At this clinic visit, however, his INR was supratherapeutic at 5.8; the only identified change in his drug therapy was the addition of gemfibrozil 600 mg twice/day, started 3 weeks earlier. The patient denied any changes in his dietary intake of vitamin K, alcohol use, or addition of nonprescription or herbal agents. Recent laboratory tests revealed no signs of thyroid abnormalities and only an insignificant elevation in his alanine aminotransferase level. His warfarin dose was decreased to 35-37.5 mg/week (a 22% reduction), and a therapeutic INR was maintained until gemfibrozil was later discontinued because of myalgia. After consecutive subtherapeutic INRs, his warfarin dose was increased to 45 mg/week and a therapeutic INR was maintained. Use of the Drug Interaction Probability Scale indicated that the likelihood of the gemfibrozil-warfarin interaction was probable. The exact mechanism of the proposed interactions between fibric acid derivatives and warfarin remains unknown but may be multifactorial through inhibition of cytochrome P450 isoenzymes, displacement from protein binding sites, or changes in coagulation factor synthesis. Regardless of the fibric acid derivative chosen, an empiric dosage reduction of 20% and close INR monitoring are warranted in patients receiving warfarin. PMID- 19476426 TI - Development of student professionalism. AB - In late 2007, the American College of Clinical Pharmacy (ACCP) charged their National StuNet Advisory Committee to formulate tenets of professionalism, with the primary goal of introducing students to essential attitudes and behaviors of professionalism. The committee's list of tenets served as a working document for the development of this White Paper. This collaborative effort of the ACCP Board of Regents and the National StuNet Advisory Committee sought to complement other published documents addressing student professionalism. The purpose of this White Paper is to enhance student understanding of professionalism, emphasizing the importance of the covenantal or "fiducial" relationship between the patient and the pharmacist. This fiducial relationship is the essence of professionalism and is a relationship between the patient and the pharmacist built on trust. This White Paper also outlines the traits of professionalism, which were developed after an extensive review of the literature on professionalism in medicine and pharmacy. The traits of professionalism identified here are responsibility, commitment to excellence, respect for others, honesty and integrity, and care and compassion. It is from these traits that student actions and behaviors should emanate. Students, pharmacy practitioners, and faculty have a responsibility to each other, to society as a whole, and to individual patients whom they serve to ensure that their words and actions uphold the highest standards of professional behavior. PMID- 19476427 TI - Tenets of professionalism for pharmacy students. PMID- 19476428 TI - Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents. AB - BACKGROUND: Neisseria meningitidis is an important cause of invasive bacterial infection in the United States, and disease rates are higher for adolescents than for the general population. Quadrivalent meningococcal conjugate vaccine is recommended for routine vaccination of adolescents and high-risk groups. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY CRM, with the licensed meningococcal conjugate vaccine, Menactra. METHODS: In this multicenter phase III study, 2180 adolescents 11-18 years of age were randomly assigned to 4 groups (1:1:1:1) to receive a single dose of 1 of 3 lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained before vaccination and 1 month after vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers after vaccination with MenACWY-CRM or Menactra were compared in noninferiority and superiority analyses. RESULTS: The hSBA geometric mean titers after MenACWY-CRM vaccination were higher than the hSBA geometric mean titers after Menactra vaccination, and criteria for superiority were met for this end point for all 4 serogroups. Also, the criteria for superiority of MenACWY-CRM, compared with Menactra, were met for the end points of proportion of subjects with postvaccination hSBA titers 1:8 and proportion of seroresponders for serogroups A, W-135, and Y. MenACWY-CRM was noninferior to Menactra for serogroup C for these end points. Reactogenicity was similar, with 64% of the MenACWY-CRM recipients and 70% of the Menactra recipients reporting mild and/or moderate solicited reactions. Neither vaccine was associated with a serious adverse event. CONCLUSIONS: MenACWY-CRM vaccine is well tolerated in adolescents and generates a stronger immune response than Menactra for all 4 serogroups. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00450437 . PMID- 19476430 TI - Coming-of-age of nucleic acid amplification tests for the diagnosis of tuberculosis. PMID- 19476429 TI - Performance of nucleic acid amplification tests for diagnosis of tuberculosis in a large urban setting. AB - BACKGROUND: A diagnosis of tuberculosis (TB) relies on acid-fast bacilli (AFB) smear and culture results. Two rapid tests that use nucleic acid amplification (NAA) have been approved by the US Food and Drug Administration for the diagnosis of TB based on detection of Mycobacterium tuberculosis from specimens obtained from the respiratory tract. We evaluated the performance of NAA testing under field conditions in a large urban setting with moderate TB prevalence. METHODS: The medical records of patients with suspected TB during 2000-2004 were reviewed. Analysis was restricted to the performance of NAA on specimens collected within 7 days after the initiation of treatment for TB. The assay's sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. RESULTS: The proportion of patients with confirmed or suspected TB whose respiratory tract specimens were tested by use of NAA increased from 429 (12.9%) of 3334 patients in 2000 to 527 (15.6%) of 3386 patients in 2004; NAA testing among patients whose respiratory tract specimens tested positive for AFB increased from 415 (43.6%) of 952 patients in 2000 to 487 (55.5%) of 877 patients in 2004 (P < .001 for both trends). Of the 16,511 patients being evaluated for pulmonary TB, 4642 (28.1%) had specimens that tested positive for AFB on smear. Of those 4642 patients, 2241 (48.3%) had NAA performed on their specimens. Of those 2241 patients, 1279 (57.1%) had positive test results. Of those 1279 patients, 1262 (98.7%) were confirmed to have TB. For 1861 (40.1%) of the 4642 patients whose specimens tested positive for AFB on smear, the NAA test had a sensitivity of 96.0%, a specificity of 95.3%, a PPV of 98.0%, and an NPV of 90.9%. For 158 patients whose specimens tested negative for AFB on smear, the NAA test had a sensitivity of 79.3%, a specificity of 80.3%, a PPV of 83.1%, and an NPV of 76.0%, respectively. For the 215 specimens that tested positive for AFB by smear, we found a sensitivity, specificity, PPV, and NPV of 97.5%, 93.6%, 95.1%, and 96.8%, respectively. A high-grade smear was associated with a better test performance. CONCLUSION: NAA testing was helpful for determining whether patients whose specimens tested positive for AFB on smear had TB or not. This conclusion supports the use of this test for early diagnosis of pulmonary and extrapulmonary TB. PMID- 19476431 TI - Herpes simplex virus type 1 DNA in human corneas: what are the virological and clinical implications? PMID- 19476432 TI - Epidemiological evidence for the role of the hemoglobin receptor, hmbR, in meningococcal virulence. AB - The distribution of the hemoglobin receptor gene (hmbR) was investigated among disease and carriage Neisseria meningitidis isolates, revealing that the gene was detected at a significantly higher frequency among disease isolates than among carriage isolates. In isolates without hmbR, the locus was occupied by the cassettes exl2 or exl3 or by a "pseudo hmbR" gene, designated exl4. The hmbR locus exhibited characteristics of a pathogenicity island in published genomes of N. meningitidis, Neisseria gonorrhoeae, and Neisseria lactamica sequence type 640. These data are consistent with a role for the hmbR gene in meningococcal disease. PMID- 19476433 TI - Prevalence and clinical consequences of herpes simplex virus type 1 DNA in human cornea tissues. AB - BACKGROUND: We determined the prevalence and clinical consequences of herpes simplex virus (HSV) type 1 (HSV-1), HSV type 2 (HSV-2), and varicella-zoster virus (VZV) in cornea tissues obtained after penetrating keratoplasty (PKP) was performed. METHODS: The excised corneas of 83 patients with a history of herpetic keratitis (HK; hereafter referred to as "patients with HK") and 367 patients without a history of HK (hereafter referred to "patients without HK") were analyzed by real-time polymerase chain reaction (PCR) and virus culture for the presence of HSV-1, HSV-2, and VZV. In addition, 273 post-PKP donor corneoscleral rims were analyzed. The medical records of the transplant patients were reviewed to determine the risk factors influencing intracorneal viral load and graft survival. RESULTS: HSV-1 was the most prevalent herpesvirus. Both the prevalence of HSV-1 and the HSV-1 DNA load were higher in the corneas of patients with HK than in those of patients without HK. The HSV-1 DNA load in the corneas of patients with HK correlated with age, the recurrence-free interval, cornea neovascularization, steroid treatment before PKP, and disease severity. Herpesvirus DNA was detected in 2 of 273 corneoscleral rims. Graft survival was inversely correlated with the corneal HSV-1 DNA load in patients with HK. CONCLUSIONS: The data presented in this study argue for the implementation of real-time HSV-1 PCR to analyze the excised corneas of patients with HK, to improve post-PKP diagnosis and therapy. Screening of donor corneal tissues for herpesviruses is redundant to prevent newly acquired post-PKP HK. PMID- 19476434 TI - High prevalence of asymptomatic plasmodium falciparum infections in a highland area of western Kenya: a cohort study. AB - BACKGROUND: Transmission of malaria in an area of hypoendemicity in the highlands of western Kenya is not expected to lead to rapid acquisition of immunity to malaria. However, the subpopulation of individuals with asymptomatic Plasmodium falciparum infection may play a significant role as an infection reservoir and should be considered in malaria-control programs. Determination of the spatiotemporal dynamics of asymptomatic subpopulations provides an opportunity to estimate the epidemiological importance of this group to malaria transmission. METHODS: Monthly parasitological surveys were undertaken for a cohort of 246 schoolchildren over 12 months. The prevalence of P. falciparum infection among 2,611 blood samples was analyzed by both microscopy and polymerase chain reaction, and infection durations were determined. RESULTS: Infection prevalence and duration (range, 1-12 months) decreased with age and altitude. The prevalence was high among pooled blood samples recovered from children aged 5-9 years (34.4%) and from those aged 10-14 years (34.1%) but was significantly lower among blood samples obtained from older children (9.1%). The prevalence decreased from 52.4% among pooled blood samples from children living at an altitude of approximately 1,430 m to 23.3% among pooled samples from children living at an altitude of 1,580 m. CONCLUSIONS: The prevalence of asymptomatic P. falciparum infection was high, with polymerase chain reaction analysis detecting a significantly greater number of infections, compared with microscopy. Our results are consistent with gradual acquisition of immunity with increasing age upon repeated infection, and they also show that the risk of malaria transmission is highly heterogeneous in the highland area. The results provide strong support for targeted malaria-control interventions. PMID- 19476435 TI - Interleukin 17 production among patients with American cutaneous leishmaniasis. AB - Interleukin 17 (IL-17) plays a critical role in inflammation and autoimmunity. Very little is known about IL-17 in protozoa infection. Here, we show that lymphocytes obtained from patients with mucosal leishmaniasis and cutaneous leishmaniasis produce higher levels of IL-17 than do lymphocytes obtained from uninfected control subjects (P<.01). There was a tendency for tissue obtained from patients with mucosal leishmaniasis to contain a higher number of cells expressing IL-17, compared with tissue obtained from patients with cutaneous leishmaniasis, and there was a direct correlation between the number of cells expressing IL-17 and the presence of cellular inflammation at the lesion site (r2 = 0.86; P<.001) These data support the role of IL-17 in the pathogenesis of the inflammatory reaction in leishmaniasis. PMID- 19476436 TI - HIV viremia and the development of AIDS-related lymphoma in patients treated with highly active antiretroviral therapy. PMID- 19476438 TI - Mitochondrial-morphology-targeted breeding of industrial yeast strains for alcohol fermentation. AB - Since mitochondrial genes are repressed under high glucose and low O2, and these conditions correspond to the conditions in which yeast cells are exposed during alcohol fermentation, the existence and structure of yeast mitochondria during alcohol fermentation have not been elucidated. Yeast mitochondria can be observed throughout brewing of sake (Japanese rice wine) and fragment during brewing. Furthermore, it has been revealed that Fis1 [fission 1 (mitochondrial outer membrane) homologue (Saccharomyces cerevisiae)], which is a transmembrane protein with its C-terminal anchor embedded in the outer membrane of mitochondria, is required for fragmentation of yeast mitochondria during sake brewing. By utilizing this knowledge, a fis1 disruptant of a sake yeast strain has been generated that has a networked mitochondrial structure throughout sake brewing. It transpired that this strain produces a high content of malate, which imparts a crisp acidic taste, during sake brewing. This strategy is a useful and a completely novel strategy towards developing a new yeast strain which produces a high content of malate in sake, and mitochondrial morphology has now emerged as a promising target for the breeding of practical industrial strains. PMID- 19476437 TI - Cumulative HIV viremia during highly active antiretroviral therapy is a strong predictor of AIDS-related lymphoma. AB - BACKGROUND: AIDS-related lymphoma contributes to significant morbidity and mortality among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). We assessed the predictive role of cumulative HIV viremia and other risk factors in the development of AIDS-related non-Hodgkin lymphoma. METHODS: Data from the Clinical Surveillance of HIV Disease (ClinSurv) study, an ongoing, observational, open cohort study of HIV-infected patients from different urban areas in Germany, were analyzed using a Cox proportional hazards model. RESULTS: In the Cox model, which comprised 6022 patients and 27,812 patient-years of follow-up while patients were receiving HAART from 1999 through 2006, cumulative HIV viremia was found to be independently associated with the risk of lymphoma (hazard ratio, [HR], 1.67 [95% confidence interval {CI}, 1.27-2.20]) (P < .001]). This association differed markedly between lymphoma subtypes. Although the association was more pronounced for Burkitt-type lymphoma (HR, 3.45 [95% CI, 1.52-7.85]) (P = .003), there was no association between cumulative HIV viremia and the incidence of primary central nervous system lymphoma (HR, 1.00 [95% CI, 0.39-2.57]) (P = .997). Other risk factors associated with an increased risk in a multivariable analysis included the latest CD4 T cell count as well as age per 10-year increment. CONCLUSIONS: Cumulative HIV viremia is an independent and strong predictor of AIDS-related lymphoma among patients receiving HAART. The influence of cumulative HIV viremia may differ between lymphoma subtypes. PMID- 19476439 TI - Stress-tolerance of baker's-yeast (Saccharomyces cerevisiae) cells: stress protective molecules and genes involved in stress tolerance. AB - During the fermentation of dough and the production of baker's yeast (Saccharomyces cerevisiae), cells are exposed to numerous environmental stresses (baking-associated stresses) such as freeze-thaw, high sugar concentrations, air drying and oxidative stresses. Cellular macromolecules, including proteins, nucleic acids and membranes, are seriously damaged under stress conditions, leading to the inhibition of cell growth, cell viability and fermentation. To avoid lethal damage, yeast cells need to acquire a variety of stress-tolerant mechanisms, for example the induction of stress proteins, the accumulation of stress protectants, changes in membrane composition and repression of translation, and by regulating the corresponding gene expression via stress triggered signal-transduction pathways. Trehalose and proline are considered to be critical stress protectants, as is glycerol. It is known that these molecules are effective for providing protection against various types of environmental stresses. Modifications of the metabolic pathways of trehalose and proline by self-cloning methods have significantly increased tolerance to baking-associated stresses. To clarify which genes are required for stress tolerance, both a comprehensive phenomics analysis and a functional genomics analysis were carried out under stress conditions that simulated those occurring during the commercial baking process. These analyses indicated that many genes are involved in stress tolerance in yeast. In particular, it was suggested that vacuolar H+-ATPase plays important roles in yeast cells under stress conditions. PMID- 19476440 TI - Salt and high blood pressure. AB - HBP (high blood pressure) is the leading risk of death in the world. Unfortunately around the world, blood pressure levels are predicted to become even higher, especially in developing countries. High dietary salt is an important contributor to increased blood pressure. The present review evaluates the association between excess dietary salt intake and the importance of a population-based strategy to lower dietary salt, and also highlights some salt reduction strategies from selected countries. Evidence from diverse sources spanning animal, epidemiology and human intervention studies demonstrate the association between salt intake and HBP. Furthermore, animal studies indicate that short-term interventions in humans may underestimate the health risks associated with high dietary sodium. Recent intervention studies have found decreases in cardiovascular events following reductions in dietary sodium. Salt intake is high in most countries and, therefore, strategies to lower salt intake could be an effective means to reduce the increasing burden of HBP and the associated cardiovascular disease. Effective collaborative partnerships between governments, the food industry, scientific organizations and healthcare organizations are essential to achieve the WHO (World Health Organization) recommended population-wide decrease in salt consumption to less than 5 g/day. In the milieu of increasing cardiovascular disease worldwide, particularly in resource-constrained low- and middle-income countries, salt reduction is one of the most cost-effective strategies to combat the epidemic of HBP, associated cardiovascular disease and improve population health. PMID- 19476441 TI - Acetylated tubulin associates with the fifth cytoplasmic domain of Na(+)/K(+) ATPase: possible anchorage site of microtubules to the plasma membrane. AB - We showed previously that NKA (Na(+)/K(+)-ATPase) interacts with acetylated tubulin resulting in inhibition of its catalytic activity. In the present work we determined that membrane-acetylated tubulin, in the presence of detergent, behaves as an entity of discrete molecular mass (320-400 kDa) during molecular exclusion chromatography. We also found that microtubules assembled in vitro are able to bind to NKA when incubated with a detergent-solubilized membrane preparation, and that isolated native microtubules have associated NKA. Furthermore, we determined that CD5 (cytoplasmic domain 5 of NKA) is capable of interacting with acetylated tubulin. Taken together, our results are consistent with the idea that NKA may act as a microtubule-plasma membrane anchorage site through an interaction between acetylated tubulin and CD5. PMID- 19476442 TI - Helicobacter pylori UreE, a urease accessory protein: specific Ni(2+)- and Zn(2+) binding properties and interaction with its cognate UreG. AB - The persistence of Helicobacter pylori in the hostile environment of the human stomach is ensured by the activity of urease. The essentiality of Ni(2+) for this enzyme demands proper intracellular trafficking of this metal ion. The metallo chaperone UreE promotes Ni(2+) insertion into the apo-enzyme in the last step of urease maturation while facilitating concomitant GTP hydrolysis. The present study focuses on the metal-binding properties of HpUreE (Helicobacter pylori UreE) and its interaction with the related accessory protein HpUreG, a GTPase involved in the assembly of the urease active site. ITC (isothermal titration calorimetry) showed that HpUreE binds one equivalent of Ni(2+) (Kd=0.15 microM) or Zn(2+) (Kd=0.49 microM) per dimer, without modification of the protein oligomeric state, as indicated by light scattering. Different ligand environments for Zn(2+) and Ni(2+), which involve crucial histidine residues, were revealed by site-directed mutagenesis, suggesting a mechanism for discriminating metal-ion specific binding. The formation of a HpUreE-HpUreG protein complex was revealed by NMR spectroscopy, and the thermodynamics of this interaction were established using ITC. A role for Zn(2+), and not for Ni(2+), in the stabilization of this complex was demonstrated using size-exclusion chromatography, light scattering, and ITC experiments. A calculated viable structure for the complex suggested the presence of a novel binding site for Zn(2+), actually detected using ITC and site directed mutagenesis. The results are discussed in relation to available evidence of a UreE-UreG functional interaction in vivo. A possible role for Zn(2+) in the Ni(2+)-dependent urease system is envisaged. PMID- 19476444 TI - The parent trap. PMID- 19476443 TI - Passive acceptance or active intervention... a choice with consequences. PMID- 19476446 TI - I'm not. PMID- 19476448 TI - Motown's violence in my ED. PMID- 19476449 TI - Lectin histochemical aspects of mucus function in the oesophagus of the reticulated python (Python reticulatus). AB - Using lectin histochemistry, the study characterizes basic functional aspects of the mucus produced by the oesophageal epithelium of the Reticulated python (Python reticulatus). Reaction staining varied as related to the two epithelium types present, containing goblet cells and ciliary cells. Remarkable intensities were achieved especially in the luminal mucus layer and the fine mucus covering the epithelial ciliary border for Con A (alpha-D-Man; alpha-D-Glc) as part of neutral glycoproteins, Limax flavus agglutinin (NeuNac = NeuNgc), emphasizing that water binding hyaluronan provides a hydrated interface conductive to the passage of material and UEA-I (alpha-L-Fuc), corroborating the view that fucose rich highly viscous mucus is helpful against mechanical stress during prey transport. PMID- 19476450 TI - Histomorphology of the proventriculus of three species of Australian passerines: Lichmera indistincta, Zosterops lateralis and Poephila guttata. AB - Histomorphology of the proventriculi of nectarivorous, granivorous and omnivorous passerines was studied. The proventriculus consisted of mucosal, submucosal, muscularis and serosal layers. Proventricular wall was thickest in omnivore, thinnest in granivore and intermediate in nectarivore. The openings of mucosal glands had a single spiral-like fold of mucosa in the omnivorous Silvereye, 2-3 spirals in the granivorous Zebra finch and 4-5 spirals in the nectarivorous Brown honeyeater. The mucosal glands were arranged in a uniform row in the wall of the organ and opened individually via a primary duct to the lumen of the proventriculus. The surface epithelial cells of the tunica mucosa contained secretory cells and the proventricular glands contained endocrine, neck and oxynticopeptic cells. The ultrastructural features of the oxynticopeptic cells changed from the oral to the aboral portion of the gland. In the oral region, the cytoplasm presented numerous, smaller (600-900 nm) homogenously dense zymogen secretory vesicles and larger (0.8-2.3 microm) pale floccular, tubular, mucin like secretory granules, few small mitochondria and RER while in the aboral portion of the gland, the cytoplasm presented numerous, large mitochondria with closely packed cristae, secondary lysosome and infolding of the basal and apical cell membrane. The tunica sub mucosa was thin with occasional large blood vessels. The tunica muscularis consisted of inner longitudinal, middle circular and outer longitudinal layers. The external tunica serosa contained large bundles of myelinated and unmyelinated axons that were possibly branches of the intestinal nerve. The structural adaptations of the proventriculi of these three species to their various diets are discussed. PMID- 19476451 TI - Effect of anti-basic fibroblast growth factor (anti-bFGF) on in vitro embryonic development in rat. AB - In this study, we aimed at the in vitro effects of anti-fibroblast growth factor 2 (anti-FGF-2 or anti-bFGF) on embryo culture in rats. In vitro effects of anti bFGF on total embryonic development were investigated in 40 rat embryos (which were divided into four groups) (obtained from five pregnant females) at 9.5 days of gestation that were cultured in whole rat serum (WRS), and in WRS+ 2.5, 5, and 10 microg/ml anti-bFGF. After 48 h of culturing, the embryos from each group were harvested to be analysed morphologically according to a morphological scoring system and biochemically to obtain the embryo protein content. The morphological score, embryo protein content, somite number and crown-rump length of embryos indicated that embryos cultured in WRS+ anti-bFGF had significant embryonic retardation. Mean morphological scores for the embryos grown in WRS, in the presence of 2.5, 5 and 10 microg anti-FGF-2 were 61.4 +/- 1.64, 46.3 +/- 8.42, 27 +/- 2.58 and 13.6 +/- 0.96 respectively. These results suggest that bFGF is very important for normal embryonic development and rat anti-bFGF neutralizes bFGF effect. PMID- 19476452 TI - First genetic insight into Libyan Tuaregs: a maternal perspective. AB - The Tuaregs are a semi-nomadic pastoralist people of northwest Africa. Their origins are still a matter of debate due to the scarcity of genetic and historical data. Here we report the first data on the mitochondrial DNA (mtDNA) genetic characterization of a Tuareg sample from Fezzan (Libyan Sahara). A total of 129 individuals from two villages in the Acacus region were genetically analysed. Both the hypervariable regions and the coding region of mtDNA were investigated. Phylogeographic investigation was carried out in order to reconstruct human migratory shifts in central Sahara, and to shed light on the origin of the Libyan Tuaregs. Our results clearly show low genetic diversity in the sample, possibly due to genetic drift and founder effect associated with the separation of Libyan Tuaregs from an ancestral population. Furthermore, the maternal genetic pool of the Libyan Tuaregs is characterized by a major "European" component shared with the Berbers that could be traced to the Iberian Peninsula, as well as a minor 'south Saharan' contribution possibly linked to both Eastern African and Near Eastern populations. PMID- 19476453 TI - Gender differences in bipolar disorder type I and II. AB - OBJECTIVE: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in- and out-patients. METHOD: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in- and out-patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. RESULTS: After adjusting for confounders, no marked differences in illness-related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12-16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16-0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22-3.27). CONCLUSION: Men and women with type I and II BD have fairly similar illness-related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium-term follow-up, females appear to have a higher hazard of recurrence than males. PMID- 19476454 TI - Concern for privacy in relation to age during physical examination of children: an exploratory study. AB - OBJECTIVES: To explore whether physicians behave differently regarding ethics and respect for privacy depending on children's age. We explored whether physician behaviours contributed to child uneasiness. STUDY DESIGN: Observational study of 21 children (0-12 years; 18 boys; mean age 3.2) undergoing evaluation for inguinal hernia. Specific physician-initiated verbal and nonverbal behaviours were coded from digital video discs of the consultations. RESULTS: Physician intrusiveness (i.e. approaching the child suddenly or in an uninvited way) during the physical examination was related to concurrent child uneasiness (r = 0.42, p < 0.06) and lasted through the postexamination phase of the consultation (r = 0.52, p < 0.01). Child mood during the examination strongly predicted postexamination mood (r = 0.69, p < 0.0001). Neither the total number of physician-initiated positive behaviours or privacy-related behaviours was associated with child age. Negative physician behaviours were strongly related to negative mood in the child (r = 0.72, p < 0.0001) at the close of the consultation. CONCLUSION: Although physicians were more likely to provide information to older than younger children, their behaviours regarding privacy did not differ by child age. We found that intrusiveness was rather common and related to child uneasiness that has implications for the ethical practice and a child's willingness to be examined. PMID- 19476455 TI - Orexins and the regulation of the hypothalamic-pituitary-testicular axis. AB - Orexins (OX), OX-A and OX-B, were initially identified as hypothalamic neuropeptides primarily involved in the control of food intake and states of arousal. Thereafter, orexins have been substantiated as putative pleiotropic regulators of a wide diversity of biological systems, including different neuroendocrine axes. Among the latter, compelling experimental evidence has recently been documented that orexins, mainly OX-A, may act at different levels of the hypothalamic-pituitary-gonadal (HPG) axis to modulate reproductive function. These actions are likely to include regulatory effects on the hypothalamic centres governing the HPG axis, as well as direct actions at the gonadal level. We review herein the experimental evidence, gathered in recent years, supporting a reproductive 'facet' of orexins, with special emphasis on our current knowledge of their patterns of expression and potential functional roles in the testis. Overall, the available data strongly suggest that, by acting at different levels of the HPG axis, orexins may operate as putative neuroendocrine and autocrine/paracrine regulators of gonadal function. PMID- 19476456 TI - Conscience and the unconscionable. PMID- 19476457 TI - Abstracts of the Eighth International Conference on Bipolar Disorder. June 25-27, 2009. Pittsburgh, Pennsylvania, USA. PMID- 19476462 TI - Fetal hydrocephalus caused by cryptic intraventricular hemorrhage. AB - Cryptic intracerebral hemorrhage as an etiological factor in fetal hydrocephalus has been postulated but not described at autopsy. Four fetuses with overt hydrocephalus diagnosed by in utero ultrasound examination were examined at autopsy at 19-22 weeks gestation. Although a hemorrhagic etiology was not evident on ultrasound, hemosiderin-containing macrophages and associated reactive changes were found to obstruct the otherwise well-formed cerebral aqueduct in all four. Coagulopathy due to thrombocytopenia was implicated in one case. Anomalies involving other parts of the body were identified in two cases, although a direct link to the hydrocephalus was not obvious. The abnormality was isolated in one case. In three cases, possible sites of hemorrhage in the ventricles were identified. This abnormality represents a significant proportion of the fetuses examined for hydrocephalus in our referral center. We discuss the importance of careful autopsy examination in the diagnosis of cryptic intracerebral hemorrhage and the implications for counseling. PMID- 19476463 TI - Mitotic epitopes are incorporated into age-dependent neurofibrillary tangles in Niemann-Pick disease type C. AB - The mechanism underlying neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) and other neurodegenerative disorders remains elusive. Niemann-Pick disease type C (NPC) is a kind of genetic neurovisceral disorder in which the intracellular sequestration of cholesterol and other lipids in neurons, NFT formation and neuronal degeneration in brain are the neuropathology hallmarks. The age of onset and progression of the disease vary dramatically. We have analyzed the hippocampus from 17 NPC cases, aged from 7 months to 55 years, to depict the temporal characteristics of NFT formation. Unexpectedly, classic NFT was observed in about 4-year-old NPC brain, suggesting that NFT is not aging dependent, and that juvenile brain neurons satisfy the requirements for NFT formation. NFT in the hippocampus of NPC was significantly increased in number with the advance of age. More importantly, multiple mitotic phase markers, which are not usually found in normal mature neurons, were abundant in the affected neurons and incorporated into NFT. The unusual activation of cdc2/cyclin B kinase and downstream mitotic indices are closely associated with the age-dependent NFT formation, signifying the contribution of abortive cell cycle to neurodegeneration. The cdc2 inhibitors may be therapeutically used for early intervention of neurodegeneration and NFT formation in NPC. PMID- 19476464 TI - Neuropathogenesis of naturally occurring encephalitis caused by Listeria monocytogenes in ruminants. AB - Listeriosis is a serious food-borne disease with increasing frequency in humans and ruminants. Despite the facts that in both hosts, listeriosis can occur as rhombencephalitis and ruminants are a reservoir of Listeria monocytogenes (LM) strains pathogenic for humans, little work has been done on the pathogenesis in ruminants. This study investigates the neuropathogenesis of listeric encephalitis in over 200 natural cases in cattle, sheep and goats by analyzing anatomical distribution, severity, bacterial load and temporal evolution of the lesions. Our results suggest that LM gains access to the brainstem of all three species via axonal migration not only along the trigeminal nerve, but also along other nerves. The ensuing encephalitis does not remain restricted to the brainstem. Rather, LM spreads further from the brainstem into rostral brain regions likely by intracerebral axonal migration. Significant differences in severity of the lesions and bacterial load were found between cattle and small ruminants, which may be caused by species-specific properties of antibacterial immune responses. As histopathological lesions of human rhombencephalitis caused by LM strongly resemble those of ruminants, the disease likely has a similar pathogenesis in both hosts. PMID- 19476466 TI - 'Real decisions' on psoriasis care from informed clinicians. PMID- 19476469 TI - Strategies to prevent type 1 diabetes. AB - Type 1 diabetes is a chronic autoimmune condition resulting from T cell-mediated destruction of the insulin-producing cells in the islets of Langerhans. Its primary cause remains unknown, but it has been established that the clinical presentation is preceded by a long prodrome. This enables individuals at high risk of disease to be identified and offers the possibility of intervention to prevent clinical disease. Many groups are working in this field, concentrating on manipulation of environmental exposures that are potential triggers of autoimmunity and on immunomodulation strategies that aim to prevent destruction of beta-cells. Some interventions have shown promising results in early trials, but effective disease prevention remains elusive. This article reviews current progress in the field. PMID- 19476471 TI - Predicting steady-state HbA1c responses to sitagliptin in patients with type 2 diabetes mellitus. AB - AIMS: To develop predictive formulas using short-term changes in glycaemic parameters [haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG)] with sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, to assess longer term steady-state changes in HbA1c. METHODS: Results from two, 12-week, double-blind studies of sitagliptin in Japanese patients with type 2 diabetes mellitus receiving once-daily sitagliptin 100 mg were used to construct linear models to develop predictive formulas based on study 1 (S1) and to validate them using study 2 (S2). HbA1c and FPG were the primary and the key secondary end point for both studies and were both used to develop predictive formulas. RESULTS: The predictive formulas using HbA1c+/-FPG results (slope of change) from week 0 to week 4 in S1 showed high correlations between fitted and observed week 12 HbA1c: for HbA1c alone R2=0.76, for HbA1c+FPG R2=0.89. When using the sitagliptin 100 mg group of S2 data set to assess the validity of the predictive formulas, high correlations for HbA1c alone (R2=0.76) and for HbA1c+FPG (R2=0.77) were also observed. Data using a lower dose (25 mg once daily) of sitagliptin also demonstrated similar results. CONCLUSIONS: The early responses (over 4 weeks) in HbA1c and FPG with sitagliptin can be used to accurately predict later responses (at week 12) in HbA1c in Japanese patients with type 2 diabetes mellitus. Additional studies applying this approach to other agents with diverse mechanisms are important. PMID- 19476472 TI - Can we prevent diabetic birth defects with micronutrients? AB - Congenital malformations are more common in infants of diabetic women than in children of non-diabetic women. The mechanisms behind diabetes-induced congenital anomalies are not known. Disturbed micronutrient metabolism, in concert with oxidative stress, has been suggested as a cause of diabetes-induced malformations by several studies. In experimental work, administration of inositol, arachidonic acid and several antioxidative compounds, as well as folic acid, to the embryo, has proven to attenuate the teratogenic effects of a diabetic environment. Future therapeutic efforts may include supplementation with antioxidants or micronutrients, such as folic acid, to the pregnant diabetic woman, although exact compounds and doses need to be determined. PMID- 19476474 TI - Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. AB - AIMS: To investigate the safety, tolerability, pharmacokinetic and pharmacodynamic properties of multiple oral doses of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (BI 1356) in patients with type 2 diabetes mellitus. METHODS: Forty-seven male type 2 diabetic patients received linagliptin 1, 2.5, 5 or 10 mg, or placebo, once daily for 12 days. RESULTS: Linagliptin exposure [area under the plasma concentration-time curve and maximum plasma concentration (Cmax)] increased less than proportionally with dose. Accumulation half-life was short (8.6-23.9 h), resulting in rapid attainment of steady state (2-5 days) and little accumulation (range: 1.18-2.03). The long terminal half life (113-131 h) led to a sustained inhibition of DPP-4 activity. Renal excretion was below 1% on day 1 in all dose groups. Inhibition of plasma DPP-4 activity correlated well with linagliptin plasma concentrations, resulting in DPP-4 inhibition >90% in the two highest dose groups; even 24 h postdose, DPP-4 inhibition was >80%. Following an oral glucose tolerance test, 24 h after the last dose, statistically significant reductions of glucose excursions were observed with linagliptin (2.5, 5 and 10 mg doses) compared with placebo. Linagliptin was well tolerated. The frequency of adverse events (AEs) was not higher with linagliptin (54%) than with placebo (75%). No serious AEs and no episodes of hypoglycaemia were reported. CONCLUSIONS: In type 2 diabetic patients, multiple rising doses of linagliptin were well tolerated and resulted in significant improvements of glucose parameters. Together with the favourable pharmacokinetics, these results confirm the unique profile of linagliptin in the DPP-4 inhibitor class. PMID- 19476470 TI - Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycaemic control comparable to rosiglitazone/metformin tablet. AB - AIM: To assess the use of a new repaglinide/metformin fixed-dose combination (FDC) tablet for the treatment of type 2 diabetes. METHODS: In this 26-week, multicentre, open-label, parallel-group trial, subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to receive a repaglinide/metformin FDC tablet either two times daily (BID) or three times daily (TID) or a rosiglitazone/metformin FDC tablet BID. The primary objective comprised two hypotheses tested in a hierarchical order: (i) that treatment with the repaglinide/metformin FDC BID is non-inferior to that of a rosiglitazone/metformin FDC tablet BID as measured by changes in haemoglobin A1c (HbA1c) (results presented here) and (ii) if true, that treatment with the repaglinide/metformin FDC BID was non-inferior to that of the repaglinide/metformin FDC TID as measured by changes in HbA1c (results presented in a companion paper). Additional efficacy and safety end-points were also assessed. RESULTS: Of the 561 subjects randomized, 383 completed the study. Reductions in HbA1c values became apparent at earlier times for repaglinide/metformin FDC BID treatment than rosiglitazone/metformin FDC BID, and final changes in HbA1c were not significantly different between treatment arms (p = 0.8186); thus, the predefined statistical criterion for non-inferiority was met. Overall adverse event profiles were comparable between treatment groups, and no major hypoglycaemic episodes were reported during the study. CONCLUSIONS: The repaglinide/metformin FDC BID regimen showed efficacy that was non-inferior to that of the rosiglitazone/metformin FDC BID regimen currently in clinical use and a more rapid reduction of HbA1c values. Thus, repaglinide/metformin FDC BID is a clinically feasible alternative to rosiglitazone/metformin FDC BID. PMID- 19476473 TI - Comparison of vildagliptin and metformin monotherapy in elderly patients with type 2 diabetes: a 24-week, double-blind, randomized trial. AB - AIMS: The study evaluated the efficacy and tolerability of the dipeptidyl peptidase-4 inhibitor, vildagliptin, and metformin in drug-naive elderly patients with type 2 diabetes. The primary objective was to demonstrate non-inferiority of vildagliptin vs. metformin in glycated haemoglobin (HbA1c) reduction. METHODS: This was a double-blind, randomized, multicentre, active-controlled, parallel group study of 24-week treatment with vildagliptin (100 mg daily, n=169) or metformin (titrated to 1500 mg daily, n=166) in drug-naive patients with type 2 diabetes aged>or=65 years (baseline HbA1c 7-9%). RESULTS: Participants had a mean age of 71 years, known duration of diabetes of 3 years and mean baseline HbA1c of 7.7%. At end-point, vildagliptin was as effective as metformin, improving HbA1c by -0.64+/-0.07% and -0.75+/-0.07%, respectively, meeting the predefined statistical criterion for non-inferiority (upper limit of 95% confidence interval for between-treatment differenceA) as compared to B*2708. The nucleotide change caused an amino acid substitution from valine (V) to glutamic acid (E) at codon 152. Since B*2740 carries sequence confers to HLA-Bw6 public epitope we believe that this novel B*27 allele might have been generated from a gene conversion involving a Bw4-specific allele (probably B*2704) and a Bw6-specific allele. PMID- 19476483 TI - The role of the CCR5 Delta32 polymorphism in abdominal aortic aneurysms. AB - BACKGROUND: C-C chemokine receptor 5 (CCR5) is involved in the regulation of the inflammatory response. Abdominal aortic aneurysms (AAA) may arise as the result of a chronic inflammatory process which is influenced by genetic predisposition. The CCR5 gene is associated with a 32 base pair deletion (the Delta32 polymorphism). The aim of this study was to investigate the role of the CCR5 Delta32 polymorphism in the development of AAA. METHODS: A case-control study was conducted including 285 patients with AAA and 273 control subjects. A blood sample was taken from each individual and DNA was extracted. CCR5 genotype was determined using the polymerase chain reaction (PCR). Flow cytometry was used to investigate the biological activity of the Delta32 polymorphism. RESULTS: There was no significant difference between the AAA and the control group in relation to the Delta32 allele frequency (AAA group 10%, control group = 12%, P = 0.82, chi-squared analysis). Genotype analysis revealed no significant difference between the groups (AAA vs. controls, wild-type homozygotes = 82% vs. 77%, heterozygotes = 16% vs. 21%, vs. Delta32 homozygotes = 2% and 2%, respectively, P = 0.33, chi-squared analysis). The polymorphism was shown to be biologically active with the number of Delta32 alleles correlating with cell expression of ccr5 as detected with flow cytometry (P < or = 0.05). CONCLUSION: This study demonstrates that the ccr5 Delta32 is a biologically active genetic polymorphism; however, there is no association between this polymorphism and AAA. PMID- 19476484 TI - Reaction mechanisms of thiamin diphosphate enzymes. PMID- 19476486 TI - Reaction mechanisms of thiamin diphosphate enzymes: new insights into the role of a conserved glutamate residue. AB - Subsequent to the demonstration in the late 1950s of the catalytic power of the C2 anion/ylid of thiamin diphosphate, further convincing evidence was provided demonstrating that the 4'-aminopyrimidine group plays a vital role in activation of this cofactor. Structural evidence from several crystal structures of thiamin diphosphate-dependent enzymes emphasized the presence of a glutamate residue in hydrogen-bonding distance from N1' as a conserved element in these enzymes. The important role of this conserved glutamate in promoting C2-H ionization and activation of thiamin diphosphate was emphasized by site-directed mutagenesis studies. This role was further elaborated by spectroscopic studies of the 4' aminopyrimidine-iminopyrimidine tautomerization. The low polarity of the environment of the protein-bound thiazolium is an additional factor in the stabilization of the C2 anion/ylid. The recently determined crystal structure and mutagenesis studies of glyoxylate carboligase, in which the position of the conserved glutamate is occupied by valine, now show that, for the multi-step reaction catalyzed by this enzyme, the advantages of accelerating the ionization of C2-H by re-introducing a carboxylate are outweighed by the apparent overstabilization of intermediates. PMID- 19476485 TI - Reaction mechanisms of thiamin diphosphate enzymes: defining states of ionization and tautomerization of the cofactor at individual steps. AB - We summarize the currently available information regarding the state of ionization and tautomerization of the 4'-aminopyrimidine ring of the thiamine diphosphate on enzymes requiring this coenzyme. This coenzyme forms a series of covalent intermediates with its substrates as an electrophilic catalyst, and the coenzyme itself also carries out intramolecular proton transfers, which is virtually unprecedented in coenzyme chemistry. An understanding of the state of ionization and tautomerization of the 4'-aminopyrimidine ring in each of these intermediates provides important details about proton movements during catalysis. CD spectroscopy, both steady-state and time-resolved, has proved crucial for obtaining this information because no other experimental method has provided such atomic detail so far. PMID- 19476487 TI - Reaction mechanisms of thiamin diphosphate enzymes: redox reactions. AB - Amongst a wide variety of different biochemical reactions in cellular carbon metabolism, thiamin diphosphate-dependent enzymes catalyze the oxidative decarboxylation of 2-keto acids. This type of reaction typically involves redox coupled acyl transfer to CoA or phosphate and is mediated by additional cofactors, such as flavins, iron-sulfur clusters or lipoamide swinging arms, which transmit the reducing equivalents that arise during keto acid oxidation to a final electron acceptor. EPR spectroscopic and kinetic studies have implicated the intermediacy of radical cofactor intermediates in pyruvate:ferredoxin oxidoreductase and an acetyl phosphate-producing pyruvate oxidase, whereas the occurrence of transient on-pathway radicals in other enzymes is less clear. The structures of pyruvate:ferredoxin oxidoreductase and pyruvate oxidase with different enzymic reaction intermediates along the pathway including a radical intermediate were determined by cryo-crystallography and used to infer electron tunneling pathways and the potential roles of CoA and phosphate for an intimate coupling of electron and acyl group transfer. Viable mechanisms of reductive acetylation in pyruvate dehydrogenase multi-enzyme complex, and of electron transfer in the peripheral membrane enzyme pyruvate oxidase from Escherichia coli, are also discussed. PMID- 19476488 TI - Typical 2-Cys peroxiredoxins--structures, mechanisms and functions. AB - Peroxiredoxins are abundant cellular antioxidant proteins that help to control intracellular peroxide levels. These proteins may also function, in part, through an evolved sensitivity of some peroxiredoxins towards peroxide-mediated inactivation in hydrogen peroxide signaling in eukaryotes. This review summarizes recent progress in our understanding of the catalytic and regulatory mechanisms of 'typical 2-Cys' peroxiredoxins and of the biological roles played by these important enzymes in oxidative stress and nonstress-related cellular signaling. New evidence suggests localized peroxide buildup plays a role in nonstress related signaling. PMID- 19476489 TI - Typical 2-Cys peroxiredoxins--modulation by covalent transformations and noncovalent interactions. AB - 2-Cys peroxiredoxins are peroxidases devoid of prosthetic groups that mediate in the defence against oxidative stress and the peroxide activation of signaling pathways. This dual capacity relies on the high reactivity of the conserved peroxidatic and resolving cysteines, whose modification embraces not only the usual thiol-disulfide exchange but also higher oxidation states of the sulfur atom. These changes are part of a complex system wherein the cooperation with other post-translational modifications - phosphorylation, acetylation - may function as major regulatory mechanisms of the quaternary structure. More importantly, modern proteomic approaches have identified the oxyacids at cysteine residues as novel protein targets for unsuspected post-translational modifications, such as phosphorylation that yields the unusual sulfi(o)nic phosphoryl anhydride. In this article, we review the biochemical attributes of 2 Cys peroxiredoxins that, in combination with complementary studies of forward and reverse genetics, have generated stimulating molecular models to explain how this enzyme integrates into cell signaling in vivo. PMID- 19476490 TI - The cartilage-specific transcription factor Sox9 regulates AP-2epsilon expression in chondrocytes. AB - Activating enhancer-binding protein (AP)-2epsilon was previously described as a new regulator of integrin alpha(10) expression in cartilage. In this study, we analyzed the expression of AP-2epsilon in differentiated chondrocytes and in human mesenchymal stem cells (HMSCs), which have been differentiated into chondrocytes in vitro. AP-2epsilon is predominantly expressed during the late stages of chondrocyte differentiation, mainly in early hypertrophic cartilage, consistent with immunohistochemical stainings of mouse embryo sections. Furthermore, osteoarthritic chondrocytes, resembling a hypertrophic phenotype, have high AP-2epsilon levels. The AP-2epsilon promoter harbors binding sites for the transcription factors AP-2alpha and Sox9. Both transcription factors strongly activate AP-2epsilon expression in a cooperative manner in the chondrosarcoma cell line SW1353. The inhibition of Sox9 expression by small interfering RNA resulted in decreased AP-2epsilon expression. In addition, direct interaction of Sox9 with the AP-2epsilon promoter could be confirmed by chromatin immunoprecipitation and electromobility shift assays. This is the first study to prove the direct regulation of AP-2epsilon by the transcription factor Sox9, and to indicate that AP-2epsilon potentially has an important role as a modulator of hypertrophic cartilage. PMID- 19476491 TI - Efficient killing of SW480 colon carcinoma cells by a signal transducer and activator of transcription (STAT) 3 hairpin decoy oligodeoxynucleotide- interference with interferon-gamma-STAT1-mediated killing. AB - The signal transducers and activators of transcription (STATs) convey signals from the membrane to the nucleus in response to cytokines or growth factors. STAT3 is activated in response to cytokines involved mostly in cell proliferation; STAT1 is activated by cytokines, including interferon-gamma, involved in defence against pathogens and the inhibition of cell proliferation. STAT3, which is frequently activated in tumour cells, is a valuable target with respect to achieving inhibition of tumour cell proliferation. Indeed, its inhibition results in cell death. We previously observed that inhibition of the transcription factor nuclear factor-kappaB, a key regulator of cell proliferation, with decoy oligodeoxynucleotides results in cell death. We used a similar approach for STAT3. A hairpin STAT3 oligodeoxynucleotide was added to a colon carcinoma cell line in which it induced cell death as efficiently as the STAT3 inhibitor stattic. The hairpin STAT3 oligodeoxynucleotide co-localized with STAT3 within the cytoplasm, prevented STAT3 localization to the nucleus, blocked a cyclin D1 reporter promoter and associated with STAT3 in pull-down assays. However, the same cells were efficiently killed by interferon-gamma. This effect was counteracted by the STAT3 oligodeoxynucleotide, which was found to efficiently inhibit STAT1. Thus, although it can inhibit STAT3, the hairpin STAT3 oligodeoxynucleotide appears also to inhibit STAT1-mediated interferon-gamma cell killing, highlighting the need to optimize STAT3-targeting oligodeoxynucleotides. PMID- 19476492 TI - Dual modulation of prothrombin activation by the cyclopentapeptide plactin. AB - Plactin, a family of cyclopentapeptides, enhances fibrinolytic activity by elevating the activity of cellular urokinase-type plasminogen activator (u-PA), a protease involved in a variety of extracellular proteolytic events. Factor(s) in the blood plasma is an absolute requirement for this plactin activity. In this study, we found that plactin promoted plasma cofactor-dependent conversion of inactive single-chain u-PA to active two-chain u-PA on U937 cells. Using plactin affinity chromatography, we identified prothrombin as one of the plasma cofactors. In incubations of U937 cells with prothrombin and Xa, plactin increased the formation of thrombin, which cleaved single-chain u-PA to afford the inactive two-chain form. Thrombin-cleaved two-chain u-PA was alternatively activated by cellular cystatin-sensitive peptidase activity, yielding fully active two-chain u-PA. In a purified system, plactin bound to prothrombin, altered its conformation and dually modulated factor Xa-mediated proteolytic activation of prothrombin to alpha-thrombin. Plactin inhibited the activation catalyzed by Xa in complex with Va, Ca(2+) and phospholipids (prothrombinase), whereas the activations catalyzed by nonmembrane-associated Xa were enhanced markedly by plactin. Plactin inhibited in vitro plasma coagulation, which involved prothrombinase formation. Plactin did not cause prothrombin activation or thrombosis in normal mice at doses that produced a protective effect in a thrombin-induced pulmonary embolism mouse model. Therefore, the dual modulation of prothrombin activation by plactin may be interpreted as leading to anticoagulation under physiological coagulating conditions. PMID- 19476493 TI - Molecular design of a nylon-6 byproduct-degrading enzyme from a carboxylesterase with a beta-lactamase fold. AB - A carboxylesterase with a beta-lactamase fold from Arthrobacter possesses a low level of hydrolytic activity (0.023 mumol.min(-1).mg(-1)) when acting on a 6 aminohexanoate linear dimer byproduct of the nylon-6 industry (Ald). G181D/H266N/D370Y triple mutations in the parental esterase increased the Ald hydrolytic activity 160-fold. Kinetic studies showed that the triple mutant possesses higher affinity for the substrate Ald (K(m) = 2.0 mm) than the wild type Ald hydrolase from Arthrobacter (K(m) = 21 mm). In addition, the k(cat)/K(m) of the mutant (1.58 s(-1).mm(-1)) was superior to that of the wild-type enzyme (0.43 s(-1).mm(-1)), demonstrating that the mutant efficiently converts the unnatural amide compounds even at low substrate concentrations, and potentially possesses an advantage for biotechnological applications. X-ray crystallographic analyses of the G181D/H266N/D370Y enzyme and the inactive S112A-mutant-Ald complex revealed that Ald binding induces rotation of Tyr370/His375, movement of the loop region (N167-V177), and flip-flop of Tyr170, resulting in the transition from open to closed forms. From the comparison of the three-dimensional structures of various mutant enzymes and site-directed mutagenesis at positions 266 and 370, we now conclude that Asn266 makes suitable contacts with Ald and improves the electrostatic environment at the N-terminal region of Ald cooperatively with Asp181, and that Tyr370 stabilizes Ald binding by hydrogen bonding/hydrophobic interactions at the C-terminal region of Ald. PMID- 19476495 TI - In vivo RNA interference in oyster--vasa silencing inhibits germ cell development. AB - This study investigated the potential of RNA interference, which is technically challenging in bivalve mollusc species, to assess gene function in the oyster Crassostrea gigas. We designed dsRNA targeting the oyster vasa-like gene (Oyvlg), specifically expressed in oyster germ cells. In vivo injection of oyvl-dsRNA into the gonad provokes a knockdown phenotype corresponding to germ cell underproliferation and prematurely arrested meiosis througout the organ. The most severe phenotype observed is sterile. This knockdown phenotype is associated with a decrease in Oyvlg mRNA level of between 39% and 87%, and a strong reduction in OYVLG protein, to an undetectable level. Therefore, Oyvlg appears to be essential for germ cell development in Crassostrea gigas, particularly for mitotic proliferation and early meiosis. Our results demonstrate for the first time that in vivo RNA interference works efficiently in a bivalve species, opening major perspectives for functional genetic studies. PMID- 19476494 TI - Activator-binding domains of the SWI/SNF chromatin remodeling complex characterized in vitro are required for its recruitment to promoters in vivo. AB - Interaction between acidic activation domains and the activator-binding domains of Swi1 and Snf5 of the yeast SWI/SNF chromatin remodeling complex has previously been characterized in vitro. Although deletion of both activator-binding domains leads to phenotypes that differ from the wild-type, their relative importance for SWI/SNF recruitment to target genes has not been investigated. In the present study, we used chromatin immunoprecipitation assays to investigate the individual and collective importance of the activator-binding domains for SWI/SNF recruitment to genes within the GAL regulon in vivo. We also investigated the consequences of defective SWI/SNF recruitment for target gene activation. We demonstrate that deletion of both activator-binding domains essentially abolishes galactose-induced SWI/SNF recruitment and causes a reduction in transcriptional activation similar in magnitude to that associated with a complete loss of SWI/SNF activity. The activator-binding domains in Swi1 and Snf5 make approximately equal contributions to the recruitment of SWI/SNF to each of the genes studied. The requirement for SWI/SNF recruitment correlates with GAL genes that are highly and rapidly induced by galactose. PMID- 19476496 TI - Adenine, a hairpin ribozyme cofactor--high-pressure and competition studies. AB - The RNA world hypothesis assumes that life arose from ancestral RNA molecules, which stored genetic information and catalyzed chemical reactions. Although RNA catalysis was believed to be restricted to phosphate chemistry, it is now established that the RNA has much wider catalytic capacities. In this respect, we devised, in a previous study, two hairpin ribozymes (adenine-dependent hairpin ribozyme 1 and adenine-dependent hairpin ribozyme 2) that require adenine as cofactor for their reversible self-cleavage. We have now used high hydrostatic pressure to investigate the role of adenine in the catalytic activity of adenine dependent hairpin ribozyme 1. High-pressure studies are of interest because they make it possible to determine the volume changes associated with the reactions, which in turn reflect the conformational modifications and changes in hydration involved in the catalytic mechanism. They are also relevant in the context of piezophilic organisms, as well as in relation to the extreme conditions that prevailed at the origin of life. Our results indicate that the catalytic process involves a transition state whose formation is accompanied by a positive activation volume and release of water molecules. In addition, competition experiments with adenine analogs strongly suggest that exogenous adenine replaces the adenine present at the catalytic site of the wild-type hairpin ribozyme. PMID- 19476497 TI - Do N-terminal nucleophile hydrolases indeed have a single amino acid catalytic center? AB - A new set of experimental kinetic data on the hydrolysis of a series of phenylacetyl p-substituted anilides catalyzed by penicillin G acylase from Escherichia coli (PGA) is presented in this article. The Hammett plot of log(k(cat,R)/k(cat,H)) versus sigma(p) (-) has three linear segments, which distinguishes the enzyme from the other N-terminal nucleophile hydrolases for which data are available. Three amino acids in the vicinity of the catalytic SerB1 (AsnB241, AlaB69, and GlnB23) were included in the quantum mechanical model. The stable structures and the transition states for acylation were optimized by molecular mechanical modeling and at the AM1 level of theory for three model substrates (with H, a methoxy group or a nitro group in the para position in the leaving group). Intrinsic interactions of several functional groups at the active site of PGA are discussed in relation to the catalytic efficiency of the enzyme. The energy barrier computed for the first step of acylation (the nucleophilic attack of SerB1) is lower than that for the second step (the collapse of the tetrahedral intermediate). However, the electronic properties of the substituent on the leaving group affect the structure of the second transition state. It is shown that the main chain carbonyl group of GlnB23 forms a hydrogen bond with the leaving group nitrogen, thus influencing the hydrolysis rate. On the basis of our computations, we propose an interpretation of the complex character of the Hammett plot for the reaction catalyzed by PGA. We suggest a modified scheme of the catalytic mechanism in which some of the intramolecular interactions essential for catalysis are included. PMID- 19476498 TI - ATP-binding domain of heat shock protein 70 is essential for its effects on the inhibition of the release of the second mitochondria-derived activator of caspase and apoptosis in C2C12 cells. AB - Hydrogen peroxide (H(2)O(2)) is a well known oxidative stress inducer causing apoptosis of many cells. Previously, we have shown that heat shock pretreatment blocked the release of the second mitochondria-derived activator of caspase (Smac) to the cytosol and inhibited apoptosis of C2C12 myoblast cells in response to H(2)O(2). The present study aimed to elucidate the underlying mechanism by over-expressing a major stress-inducible protein, heat shock protein (HSP) 70, and characterizing the resulting cellular changes. We demonstrate that HSP70 over expression markedly inhibited the release of Smac and prevented the activation of caspases-9 and -3 and apoptosis in C2C12 cells under H(2)O(2) treatment. However, no direct interaction between HSP70 and Smac was observed by co immunoprecipitation. Mutational analysis demonstrated that the ATP-binding domain of HSP70, rather than the peptide-binding domain, was essential for these observed HSP functions. Taken together, our results provide evidence supporting the role of HSP70 in the protection of C2C12 cells from H(2)O(2)-induced and Smac promoted apoptosis by preventing the release of Smac from mitochondria, thereby inhibiting activation of caspases-9 and -3. This mechanism of HSP70 action is dependent on its ATP-binding domain but independent of its interaction with Smac protein. PMID- 19476499 TI - Untangling the folding mechanism of the 5(2)-knotted protein UCH-L3. AB - Proteins possessing deeply embedded topological knots in their structure add a stimulating new challenge to the already complex protein-folding problem. The most complicated knotted topology observed to date belongs to the human enzyme ubiquitin C-terminal hydrolase UCH-L3, which is an integral part of the ubiquitin proteasome system. The structure of UCH-L3 contains five distinct crossings of its polypeptide chain, and it adopts a 5(2)-knotted topology, making it a fascinating target for folding studies. Here, we provide the first in depth characterization of the stability and folding of UCH-L3. We show that the protein can unfold and refold reversibly in vitro without the assistance of molecular chaperones, demonstrating that all the information necessary for the protein to find its knotted native structure is encoded in the amino acid sequence, just as with any other globular protein, and that the protein does not enter into any deep kinetic traps. Under equilibrium conditions, the unfolding of UCH-L3 appears to be two-state, however, multiphasic folding and unfolding kinetics are observed and the data are consistent with a folding pathway in which two hyperfluorescent intermediates are formed. In addition, a very slow phase in the folding kinetics is shown to be limited by proline-isomerization events. Overall, the data suggest that a knotted topology, even in its most complex form, does not necessarily limit folding in vitro, however, it does seem to require a complex folding mechanism which includes the formation of several distinct intermediate species. PMID- 19476500 TI - Construction of a novel detection system for protein-protein interactions using yeast G-protein signaling. AB - In the current study, we report the construction of a novel system for the detection of protein-protein interactions using yeast G-protein signaling. It is well established that the G-protein gamma subunit (Ggamma) is anchored to the inner leaflet of the plasma membrane via lipid modification in the C-terminus, and that this localization of Ggamma is required for signal transduction. In our system, mutated Ggamma (Ggamma(cyto)) lacking membrane localization ability was genetically prepared by deletion of the lipid modification site. Complete disappearance of G-protein signal was observed when Ggamma(cyto) was expressed in the cytoplasm of yeast cells from which the endogenous Ggamma gene had been deleted. In order to demonstrate the potential use of our system, we utilized the Staphylococcus aureus ZZ domain and the Fc portion of human immunoglobulin G (IgG) as a model interaction pair. To design our detection system for protein protein interaction, the ZZ domain was altered so that it associates with the inner leaflet of the plasma membrane, and the Fc part was then fused to Ggamma(cyto). The Fc-Ggamma(cyto) fusion protein migrated towards the membrane via the ZZ-Fc interaction, and signal transduction was therefore restored. This signal was successfully detected by assessing growth inhibition and transcription in response to G-protein signaling. Finally, several Z variants displaying affinity constants ranging from 8.0 x 10(3) to 6.8 x 10(8) m(-1) were prepared, and it was demonstrated that our system was able to discriminate subtle differences in affinity. In conclusion, our system appears to be a reliable and versatile technique for detection of protein-protein interactions, and may prove useful in future protein interaction studies. PMID- 19476501 TI - Regulation of secretases by all-trans-retinoic acid. AB - One of the emerging approaches for the treatment of Alzheimer's disease aims at reducing toxic levels of Alphabeta-species through the modulation of secretases, namely by inducing alpha-secretase or inhibiting beta-secretase and/or gamma secretase activities, or a combination of both. Although there is increasing evidence for the involvement of retinoids in Alzheimer's disease, their significance in the regulation of Alphabeta-peptide production remains unresolved. Our work concentrated on the regulation of all secretases mediated by all-trans-retinoic acid (ATRA), and supports the hypothesis that ATRA is capable of regulating them in an antiamyloidogenic sense at the levels of transcription, translation, and activation. Apart from increased alpha-secretase activity, we show a complex chain of regulatory events, resulting in impaired beta-secretase trafficking and membrane localization upon protein kinase C (PKC) activation by ATRA. Furthermore, ATRA demonstrates substrate specificity for beta-site amyloid precursor protein-cleaving enzyme (BACE) 1 over nonamyloidogenic BACE2 in beta secretase regulation, which probably promotes competition for amyloid precursor protein between ADAM17 and BACE1. Additionally, we report enhanced secretion of soluble amyloid precursor protein alpha after ATRA exposure, possibly due to PKC activation, as pretreatment with the PKC inhibitor Go6976 abolished all these events. PMID- 19476502 TI - The DRD2 TaqIA polymorphism associated with changed midbrain volumes in healthy individuals. AB - The human DRD2 gene is located on chromosome 11q22-q23 and contains one specific functional polymorphism called TaqIA, which characteristically presents two alleles referred to as A1 and A2. Evidence indicates that the A1 allele impacts brain dopaminergic function and may confer an increased risk of developing Parkinson's disease. However, possible morphological changes underlying such genetic variant remain to be clarified. The aim of this study was to provide an in vivo demonstration of changes in brain structures associated with the TaqIA polymorphism of the DRD2 gene. Optimized voxel-based morphometry (VBM) was applied to high-resolution MR brain images of 70 healthy controls divided into two groups according to their DRD2 genotype (A1/A2, n = 15; A2/A2, n = 55). Compared with individuals' homozygous for the A2 allele, the A1 carriers had significantly smaller areas of a specific part of the midbrain, encompassing the substantia nigra bilaterally. Our findings showed an association of the DRD2 TaqIA polymorphism with the changed volumes of a specific subcortical region strongly involved in the dopaminergic system. PMID- 19476503 TI - Biogeochemical changes induced in uranium mining waste pile samples by uranyl nitrate treatments under anaerobic conditions. AB - Response of the subsurface soil bacterial community of a uranium mining waste pile to treatments with uranyl nitrate over different periods of time was studied under anaerobic conditions. The fate of the added U(VI) without supplementation with electron donors was investigated as well. By using 16S rRNA gene retrieval, we demonstrated that incubation with uranyl nitrate for 4 weeks resulted in a strong reduction in and even disappearance of some of the most predominant bacterial groups of the original sample. Instead, a strong proliferation of denitrifying and uranium-resistant populations of Rahnella spp. from Gammaproteobacteria and of Firmicutes occurred. After longer incubations for 14 weeks with uranyl nitrate, bacterial diversity increased and populations intrinsic to the untreated samples such as Bacteroidetes and Deltaproteobacteria propagated and replaced the above-mentioned uranium-resistant groups. This indicated that U(VI) was immobilized. Mossbauer spectroscopic analysis revealed an increased Fe(III) reduction by increasing the incubation time from four to 14 weeks. This result signified that Fe(III) was used as an electron acceptor by the bacterial community established at the later stages of the treatment. X-ray absorption spectroscopic analysis demonstrated that no detectable amounts of U(VI) were reduced to U(IV) in the time frames of the performed experiments. The reason for this observation is possibly due to the low level of electron donors in the studied oligotrophic environment. Time-resolved laser-induced fluorescence spectroscopic analysis demonstrated that most of the added U(VI) was bound by organic or inorganic phosphate phases both of biotic origin. PMID- 19476504 TI - Bacterial formation of phosphatic laminites off Peru. AB - Authigenic phosphatic laminites enclosed in phosphorite crusts from the shelf off Peru (10 degrees 01' S and 10 degrees 24' S) consist of carbonate fluorapatite layers, which contain abundant sulfide minerals including pyrite (FeS(2)) and sphalerite (ZnS). Low delta(34)S(pyrite) values (average -28.8 per thousand) agree with bacterial sulfate reduction and subsequent pyrite formation. Stable sulfur isotopic compositions of sulfate bound in carbonate fluorapatite are lower than that of sulfate from ambient sea water, suggesting bacterial reoxidation of sulfide by sulfide-oxidizing bacteria. The release of phosphorus and subsequent formation of the autochthonous phosphatic laminites are apparently caused by the activity of sulfate-reducing bacteria and associated sulfide-oxidizing bacteria. Following an extraction-phosphorite dissolution-extraction procedure, molecular fossils of sulfate-reducing bacteria (mono-O-alkyl glycerol ethers, di-O-alkyl glycerol ethers, as well as the short-chain branched fatty acids i/ai-C(15:0), i/ai-C(17:0) and 10MeC(16:0)) are found to be among the most abundant compounds. The fact that these molecular fossils of sulfate-reducing bacteria are distinctly more abundant after dissolution of the phosphatic laminite reveals that the lipids are tightly bound to the mineral lattice of carbonate fluorapatite. Moreover, compared with the autochthonous laminite, molecular fossils of sulfate reducing bacteria are: (1) significantly less abundant and (2) not as tightly bound to the mineral lattice in the other, allochthonous facies of the Peruvian crusts consisting of phosphatic coated grains. These observations confirm the importance of sulfate-reducing bacteria in the formation of the phosphatic laminite. Model calculations highlight that organic matter degradation by sulfate reducing bacteria has the potential to liberate sufficient phosphorus for phosphogenesis. PMID- 19476505 TI - CaCO3 nucleation by cyanobacteria: laboratory evidence for a passive, surface induced mechanism. AB - Calcite nucleation on the surface of cyanobacteria of the Synechococcus leopoliensis strain PCC 7942 was investigated to assess the influence of photosynthetic uptake of inorganic carbon and active ion exchange processes across the cell membrane on the nucleation and precipitation mechanisms. We performed long-term precipitation experiments at a constant CO(2) level in ambient air by adding suspensions of previously washed cyanobacteria to solutions of NaHCO(3)/CaCl(2) which were supersaturated with respect to calcite. Induction times between 4 and 110 h were measured over a range of saturation states, Omega, between 8 and 4. The kinetics of CaCO(3) nucleation was compared between experiments: (i) with ongoing photosynthesis, (ii) with cells metabolizing but not undergoing photosynthetic uptake of inorganic carbon and (iii) in darkness without photosynthesis. No significant differences were observed between the three treatments. The results reveal that under low nutrient concentrations and permanent CO(2) supply, photosynthetic uptake of inorganic carbon predominantly uses CO(2) and consequently does not directly influence the nucleation process of CaCO(3) at the surface of S. leopoliensis. Furthermore, ion exchange processes did not affect the kinetics, indicating a passive nucleation process wherein the cell surface or extracellular polymers provided preferential sites for mineral nucleation. The catalyzing effect of the cyanobacteria on calcite nucleation was equivalent to a approximately 18% reduction in the specific interfacial free energy of the calcite nuclei. This result and the ubiquitous abundance of cyanobacteria suggest that this process may have an impact on local and global carbon cycling. PMID- 19476506 TI - A hypersaline microbial mat from the Pacific Atoll Kiritimati: insights into composition and carbon fixation using biomarker analyses and a 13C-labeling approach. AB - Modern microbial mats are widely recognized as useful analogs for the study of biogeochemical processes relevant to paleoenvironmental reconstruction in the Precambrian. We combined microscopic observations and investigations of biomarker composition to investigate community structure and function in the upper layers of a thick phototrophic microbial mat system from a hypersaline lake on Kiritimati (Christmas Island) in the Northern Line Islands, Republic of Kiribati. In particular, an exploratory incubation experiment with (13)C-labeled bicarbonate was conducted to pinpoint biomarkers from organisms actively fixing carbon. A high relative abundance of the cyanobacterial taxa Aphanocapsa and Aphanothece was revealed by microscopic observation, and cyanobacterial fatty acids and hydrocarbons showed (13)C-uptake in the labeling experiment. Microscopic observations also revealed purple sulfur bacteria (PSB) in the deeper layers. A cyclic C(19:0) fatty acid and farnesol were attributed to this group that was also actively fixing carbon. Background isotopic values indicate Calvin Benson cycle-based autotrophy for cycC(19:0) and farnesol-producing PSBs. Biomarkers from sulfate-reducing bacteria (SRB) in the top layer of the mat and their (13)C-uptake patterns indicated a close coupling between SRBs and cyanobacteria. Archaeol, possibly from methanogens, was detected in all layers and was especially abundant near the surface where it contained substantial amounts of (13)C-label. Intact glycosidic tetraether lipids detected in the deepest layer indicated other archaea. Large amounts of ornithine and betaine bearing intact polar lipids could be an indicator of a phosphate-limited ecosystem, where organisms that are able to substitute these for phospholipids may have a competitive advantage. PMID- 19476507 TI - Roles of Sall4 in the generation of pluripotent stem cells from blastocysts and fibroblasts. AB - Pluripotency of embryonic stem (ES) cells is maintained by a network consisting of multiple transcription factors, including Oct3/4, Sox2, Nanog, Klf4 and Sall4. Among these factors, the forced expressions of Oct3/4, Sox2 and Klf4 are sufficient to reprogram fibroblasts into induced pluripotent stem (iPS) cells. The current study analyzed the role of Sall4 during the generation of ES cells and iPS cells. The mouse Sall4 gene was deleted by homologous recombination. Sall4-null embryos died shortly after implantation, as has been reported. ES-like cell lines can be established from Sall4-null blastocysts, albeit with a lower efficiency and a slower time course. The knockdown of Sall4 significantly decreased the efficiency of iPS cell generation from mouse fibroblasts. Furthermore, retroviral transduction of Sall4 significantly increased the efficiency of iPS cell generation in mouse and some human fibroblast lines. These results demonstrated that Sall4 plays positive roles in the generation of pluripotent stem cells from blastocysts and fibroblasts. PMID- 19476508 TI - Assessment of haemophilia treatment practice pattern in Japan. AB - The current status of replacement therapy for haemophilia and the role played by nurses in Japan were investigated at 16 facilities (17 specialties) each providing care to 20 or more haemophilia A or B patients without inhibitor. The questionnaire was mailed to the nurse or physician in charge of haemophilia at each facility in August 2006, asking the nurse to fill in the questionnaire. Responses were collected on 1318 patients (haemophilia A: 1078 patients; haemophilia B: 240 patients). About 70% of these patients were reported to be severe haemophilia A or B. Overall, 26% were receiving regular prophylaxis while 74% received on-demand therapy with or without temporary prophylaxis before special events. The percentage of patients receiving primary prophylaxis was only 2%. The percentage of adherence to prophylaxis decreased with age (lowest at age 19-29) but this percentage for each age group in Japan was higher than that in the western countries. Of the nurses working at the facilities surveyed, 88% considered prophylaxis as an optimal therapy for severe haemophilia patients, although the percentage of patients receiving prophylaxis for the entire population surveyed was lower than that in the western countries. The main factor precluding introduction of prophylaxis was 'difficulty in venous access' for infants and small children. On the other hand, 'unwillingness of family members' and 'poor adherence' were the main factors precluding introduction of this therapy for those aged over 6 years. PMID- 19476509 TI - Home therapy and the effect of educational programmes in Iran; an alternative treatment option in developing countries. PMID- 19476510 TI - Following TRAIL's path in the immune system. AB - The members of the tumour necrosis factor (TNF) superfamily of cytokines play important roles in the regulation of various immune-cell functions. Likewise, induction of cell death by apoptosis is indispensable for the normal functioning of the immune system. There are two major pathways of apoptosis induction. The intrinsic, or mitochondrial, pathway is regulated by the activation and interaction of members of the Bcl-2 family. The extrinsic, or death receptor, pathway is triggered by certain TNF family members when they engage their respective cognate receptors on the surface of the target cell. Hence, cell-to cell-mediated death signals are induced by activation of these death receptor ligand systems. Besides TNF itself and the CD95 (Fas/APO-1) ligand (FasL/Apo1L), the TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) belongs to the subfamily of ligands that is responsible for extrinsic induction of cell death. Depending on their status of stimulation, TRAIL can be expressed by various cells of the immune system, amongst them natural killer (NK) cells, T cells, natural killer T cells (NKT cells), dendritic cells and macrophages. TRAIL has been implicated in immunosuppressive, immunoregulatory and immune-effector functions. With respect to pathological challenges, TRAIL and its receptors have been shown to play important roles in the immune response to viral infections and in immune surveillance of tumours and metastases. In this review we summarize the current knowledge on the role of TRAIL and its receptors in the immune system and, based on this, we discuss future directions of research into the diverse functions of this fascinating receptor-ligand system. PMID- 19476511 TI - Genetic and epigenetic networks controlling T helper 1 cell differentiation. AB - Significant progress has been made during the past years in our understanding of the mechanisms that control the differentiation of naive CD4(+) T cells into effector T-cell subsets with distinct functional properties. Previous work allowed the identification of key molecules involved in regulating this highly complex process, such as cytokines and their receptors, signal transducers and transcription factors. More recently, the emphasis of research in this field has been to elucidate how the multiplicity of signals is integrated to shape a T helper subset-specific gene-expression program controlling differentiation and effector functions. In this review we will highlight advances that have been made in unravelling the genetic and epigenetic networks controlling differentiation of naive CD4(+) T cells into interferon-gamma(IFN-gamma)-secreting T helper type 1 (Th1) cells. PMID- 19476512 TI - Endosomal processing for antigen presentation mediated by CD1 and Class I major histocompatibility complex: roads to display or destruction. AB - The presentation of antigen in a form that can be recognized by T lymphocytes of the immune system requires antigen processing and association of antigen-derived fragments with molecules encoded by the major histocompatibility complex (MHC) locus or by the CD1 locus. Much emphasis on antigen processing and presentation in the last decades has focused on what we consider 'conventional routes' of antigen processing and presentation, whereby extracellular antigens are processed for presentation via Class II MHC complexes and cytosolic antigens are presented as peptide-Class I MHC complexes. We here highlight two other pathways in myeloid dendritic cells, those of lipid antigen presentation in association with CD1 and of peptide cross-presentation via Class I MHC complexes. Some pathogens evade immune recognition through inhibition of antigen presentation of phagosomal origin. Deviations in endosomal antigen processing and presentation are also seen in individuals suffering from glycosphingolipid lysosomal lipid storage diseases. We summarize recent developments in the endosomal antigen processing and presentation pathway, for display as lipid-CD1 complexes to natural killer T cells and as peptide-Class I MHC complexes to CD8 T cells. PMID- 19476513 TI - c-Maf increases apoptosis in peripheral CD8 cells by transactivating Caspase 6. AB - In addition to transactivation of interleukin-4 (IL-4), cellular muscular aponeurotic fibrosarcoma (c-Maf) enhances CD4 cell apoptosis by limiting Bcl-2 expression. The CD8 cells also express c-Maf and peripheral CD8 cell numbers are reduced in c-Maf transgenic mice, suggesting that c-Maf may influence CD8 cell survival in a manner similar to CD4 cells. Here we confirm that, similar to CD4 cells, c-Maf enhances CD8 cell susceptibility to apoptosis induced by multiple stimuli, independent of IL-4. However, unlike CD4 cells, c-Maf enhancement of apoptosis is independent of Bcl-2, suggesting that c-Maf uses other mechanisms to regulate CD8 cell apoptosis. Real-time reverse transcription-polymerase chain reaction reveals that the pro-apoptotic gene Caspase 6 is upregulated in c-Maf transgenic CD8 cells, suggesting that Caspase 6 is a novel c-Maf target gene. Luciferase reporter assays and site-directed mutagenesis reveal a functional c Maf recognition element (MARE) within the first intron of Caspase 6. Binding of c Maf to the MARE site is detectable by chromatin immunoprecipitation using non transgenic T-cell lysates, so c-Maf can interact with the Caspase 6 MARE site in normal T cells. Furthermore, caspase 6 activity is increased among CD8 cells from c-Maf transgenic mice following T-cell receptor engagement. As expected, activity of the downstream caspases 3 and 7 is also increased. Consistent with the ability of caspase 6 to participate in positive feedback loops, cytochrome c release and caspase 8 activation are also increased. Together these results indicated that c Maf increases CD8 cell sensitivity to apoptotic stimuli, at least in part, by direct transactivation of Caspase 6, providing increased substrate for Caspase 6 dependent apoptosis pathways. PMID- 19476516 TI - Dentists' involvement in identification and reporting of child physical abuse: Jordan as a case study. AB - OBJECTIVES: The objectives of this study were to assess the knowledge, attitude, and experience among Jordanian dentists regarding child abuse, and to explore the factors that affect their hesitation to report any suspected cases. MATERIALS AND METHODS: A self-administered structured questionnaire was sent randomly to 500 Jordanian dentists. It investigated dentists' knowledge, attitude, and experience in recognizing and reporting child abuse cases. It also investigated several factors associated with dentists' hesitation to report suspected cases of child physical abuse. RESULTS: The response rate was 68%. More dentists were aware of their ethical obligations (80%) than their legal responsibilities (71%) to report child abuse cases. One-third of the dentists knew where to report suspected cases. Although 42% of dentists suspected cases of child abuse, only 20% of them reported these cases. The most frequently cited reasons for hesitation to report such cases were lack of history (76%), uncertainty about diagnosis (73%), and possible consequences on the child (66%). Reporting was significantly associated with suspicion of child abuse cases, as well as the belief of legal responsibilities. CONCLUSION: There was a low reporting rate of child abuse among Jordanian dentists. They lack the adequate knowledge about recognition and reporting issues of suspected cases. PMID- 19476514 TI - Mannan-binding lectin deficiency modulates the humoral immune response dependent on the genetic environment. AB - Mannan-binding lectin (MBL) is a plasma protein implicated in innate immune defence against a broad range of microorganisms, including viruses. It is also thought that MBL plays a role in the recruitment of the specific clonal immune response. This was studied by injecting soluble hepatitis B surface antigen (HBsAg) intravenously into mice deficient in both MBL-A and MBL-C (MBL DKO mice). The MBL DKO animals on mixed genetic background (SV129EvSv x C57BL/6) produced higher antibody titres than the wild-type littermates. After primary challenge with the antigen the immunoglobulin M anti-HBsAg antibody titres were threefold higher in the MBL DKO mice than in the wild-type mice. Following the boost, the immunoglobulin G anti-HBsAg antibody titres were 10-fold higher in the MBL DKO mice, suggesting that MBL plays a role in a negative feedback regulation of adaptive immunity. However, the modulating effect of MBL was dependent on the genetic environment. The MBL DKO mice backcrossed on a C57BL/6 background showed the opposite response with the MBL DKO mice now producing fewer antibodies than the wild-type animals, whereas MBL deficiency in mice with the SV129EvSv background did not show any effect in antibody production. These findings indicate that the modifying effect of MBL on the humoral immune response is influenced by the genetic environment. PMID- 19476517 TI - Expression of heat shock protein 105 and 70 in malignant melanoma and benign melanocytic nevi. AB - BACKGROUND: Heat shock proteins (HSPs) restore immature proteins or denatured proteins, thus protecting cells. Also, the expression of some HSPs is elevated substantially in malignant tumors, but the expression of HSPs in association with melanoma has yet to be studied. Therefore, we examined the expression patterns of HSP 70 and 105 in melanoma, benign melanocytic nevi and normal human skin. METHODS: Two specimens of malignant melanoma, two of benign melanocytic nevi and six of normal human skin were analyzed using Western blot analysis for expression of HSP 70 and 105. In another set, 16 specimens of malignant melanoma, 24 of benign melanocytic nevi and eight of normal human skin were analyzed for the expression of HSP 105 using immunohistochemical studies. RESULTS: The Western blot analysis showed that HSP 70 was overexpressed in all three types. But, the HSP 105 was hardly expressed in normal human skin and benign melanocytic nevi. However, in malignant melanoma, the HSP 105 was overexpressed, and immunohistochemical examination of HSP 105 showed a result similar to that of Western blot analysis. CONCLUSIONS: In our study, HSP 105 is thought to be a more relevant tumor-associated antigen in malignant melanoma than is HSP 70. PMID- 19476518 TI - Reduction in QSART and vasoactive intestinal polypeptide expression in the skin of Parkinson's disease patients and its relation to dyshidrosis. AB - BACKGROUND: With regards to dyshidrosis in Parkinson's disease (PD), there is no established and consistent view on the occurrence sites, frequency and etiology, although there have been several reports on hypohidrosis of the limbs and sudoresis on the face/cervical region. METHODS: Hydrosis in the forearms of PD patients and healthy individuals were compared by quantitative sudomotor axon reflex test (QSART). The expression of various neuropeptides and alpha-synuclein was examined with immunohistochemical staining. RESULTS: There was a significant reduction in QSART of PD patients but not of healthy controls. Reduced expression of vasoactive intestinal polypeptide (VIP) was also detected in the sweat glands of PD patients. CONCLUSION: Reduction in QSART and VIP expression in the sweat glands might be involved in the dyshidrosis of PD patients. PMID- 19476519 TI - Beta-adrenoceptor blockade delays granulation tissue formation in polyurethane sponge implants. AB - BACKGROUND: The role of adrenoceptors in granulation tissue formation is not well understood. The aim of this study was to investigate the effects of alpha- and beta-adrenoceptor blockade on granulation tissue development using polyurethane (PU) implants in the rat. METHODS: Animals were treated orally with propranolol (beta1- and beta2-antagonist), atenolol (beta1-antagonist) or phentolamine (alpha1- and alpha2-antagonist) until euthanasia. The control group received only water. All animals received subcutaneous implants of PU sponges. After 14 days, implants were collected, formalin-fixed and paraffin-embedded. Sections were stained with hematoxylin and eosin and Sirius red and immunostained for CD68 and alpha-smooth muscle actin. RESULTS: The number of inflammatory cells and the volume density of myofibroblasts and blood vessels were lower in the control group than in the propranolol- and atenolol-treated groups. The collagen fiber score was greater in the control group than in the propranolol- and atenolol treated groups. The inflammatory infiltrate, collagen fiber score, blood vessel density or myofibroblast differentiation was not affected by phentolamine. The percentage of fibrovascular invasion was greater in the antagonist-treated groups than in the control group. CONCLUSIONS: Blockade of beta1- and beta2 adrenoceptors, but not alpha-adrenoceptors, impairs granulation tissue development in PU implants due to interference with the inflammatory response. PMID- 19476520 TI - Differential expression of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease and apocrine nevus. AB - BACKGROUND: Apocrine carcinomas are rare, the immunohistochemical characterizations that are incomplete. The purpose of this study was to determine the immunohistochemical characteristics of mucin core proteins and keratins in apocrine carcinoma, extramammary Paget's disease (EMPD) and apocrine nevus. METHODS: We report four cases of apocrine carcinomas along with immunohistochemical analyses: (i) an axillary apocrine carcinoma with an apocrine nevus, (ii) an inguinal apocrine carcinoma, (iii) a vulvar apocrine carcinoma with EMPD and (iv) an axillary apocrine carcinoma with EMPD and an apocrine nevus. RESULTS: The tumor cells of apocrine carcinomas, EMPD and apocrine nevi displayed a positive reaction to MUC-1 and CK7 and a negative reaction to CK20. Apocrine carcinomas had high molecular weight (HMW) cytokeratin(+)/CK5(+)/CK14( )/MUC5AC(-), EMPD with underlying apocrine carcinoma had HMW cytokeratin(-)/CK5( )/CK14(-)/MUCA5AC(-) and the apocrine nevi had HMW cytokeratin(+)/CK5(+)/CK14(+)/MUCA5AC(+). CONCLUSION: The immunohistochemical findings suggest that apocrine carcinomas, apocrine nevi and EMPD with underlying apocrine carcinomas are quite different, even though they are all derived from apocrine glands. PMID- 19476521 TI - Keloidal atypical fibroxanthoma: a case series. AB - BACKGROUND: Keloidal atypical fibroxanthoma (AFX) is a rare variant of AFX with thick bands of hyalinized collagen. The identification of keloidal collagen associated with fibrohistiocytic cells may erroneously lead to the diagnosis of keloidal dermatofibroma. Although AFX is a pleomorphic cutaneous tumor typically associated with a good prognosis, occasional reports of metastatic AFX highlight the importance of accurate identification. METHODS: A total of nine cases of an unusual variant of AFX with keloidal tumoral sclerosis were collected and examined. The cases were stained with antibodies directed against S100, cytokeratin, CD68 and CD31. RESULTS: Histopathological examination revealed pleomorphic cells trapped within hyalinized keloidal collagen bands. In several cases, the keloidal collagen also formed ring-shaped structures surrounding CD31 positive vascular structures. Pleomorphic cells were negative for S100 protein and keratin, but consistently labeled with antibodies directed against CD68. CONCLUSIONS: The diagnosis of keloidal AFX requires the exclusion of other malignant and benign lesions with keloidal or sclerotic collagen. Awareness of the rare variant of keloidal AFX may avoid a diagnostic pitfall leading to an erroneous diagnosis, particularly in small biopsies. The finding of sclerotic collagen preferentially deposited around vessels is an interesting and poorly understood phenomenon. PMID- 19476522 TI - Utility of p63 in the differential diagnosis of atypical fibroxanthoma and spindle cell squamous cell carcinoma. AB - Atypical fibroxanthoma (AFX), spindle cell squamous cell carcinoma (SCSCC) and spindle cell melanoma are the primary entities in the differential diagnosis of a cytologically atypical spindle cell tumor arising on sun-damaged skin. AFX is generally regarded as a diagnosis of exclusion in this context: in the absence of S100 or keratin reactivity, a diagnosis of AFX is favored. However, keratin reactivity may be focal or even absent in SCSCC, and although numerous positive markers of AFX have been proposed, none has shown sufficient sensitivity and specificity for routine diagnostic use. We evaluated 20 AFX and 10 SCSCC with a panel of cytokeratins and p63 to assess the utility of the latter antibody in this differential diagnosis. All 10 SCSCC showed strong expression of p63, whereas all 20 AFX were p63 negative. Two additional cases (excluded from the study) were negative for keratins and S100 on initial shave biopsies, resulting in a favored diagnosis of AFX, but p63 stains performed retrospectively were positive. However, review of the excision specimens in both cases revealed deep subcutaneous extension, excluding AFX. p63 reactivity argues against the diagnosis of AFX and is therefore a useful addition to the standard immunohistochemical panel for cutaneous spindle cell neoplasms. PMID- 19476523 TI - Sclerotic bodies in nephrogenic systemic fibrosis: a new histopathologic finding. AB - Nephrogenic systemic fibrosis (NSF--known previously as nephrogenic fibrosing dermopathy) is a systemic disorder observed exclusively in patients with a history of kidney disease associated with renal failure. Reported histopathologic findings of NSF include spindle-shaped fibroblast-like cells with fibrosis, thickened collagen bundles with surrounding spindled and epithelioid cells, increased number of elastic fibers, sparse inflammatory infiltrate and increased stromal mucin. Two populations of multinucleated giant cells (Factor XIIIa and CD68 positive) have also been observed. We observed the presence of sclerotic bodies with entrapped elastic fibers in two cases of NSF, which we interpreted to be collagenous in nature, a finding not previously reported. These bodies should not be confused with osseous metaplasia previously seen in association with NSF, which show lacunae and cells within the osseous bodies that may or may not be calcified. We did not observe lacunae or cells within the sclerotic bodies in our cases. Furthermore, the sclerotic bodies in our cases stained blue on Masson trichrome, whereas previous investigators observed the osseous metaplasia to be red. We suggest that sclerotic bodies may be an additional clue to the diagnosis of NSF. PMID- 19476524 TI - Simple non-staining method to demonstrate urate crystals in formalin-fixed, paraffin-embedded skin biopsies. AB - BACKGROUND: Gouty tophi classically occur as nodules over joints and the helix. The ideal fixative for preservation of gout crystals has traditionally been alcohol because the crystals are formalin and water soluble. However, most biopsies are submitted in formalin fixative, which results in dissolution of urate crystals leaving behind a non-specific pale amorphous area. Although complex staining methods to show urate crystals in tissue have been described, the present study elucidates a simple non-staining method utilizing a thick unstained coverslipped microscopy slide that allows detection and confirmation of birefringence of urate crystals in formalin-fixed, paraffin-embedded tissue. METHODS: Twenty-nine cases of cutaneous gouty tophi were evaluated using a hematoxylin-eosin (H&E)-stained section, a 10-microm unstained coverslipped section and a 4-microm unstained coverslipped section. In all cases, the specimen was received and submitted in formalin. RESULTS: Polarizable crystals were not identified in any of the H&E sections. The use of the thicker unstained coverslipped section was more sensitive than the standard 4 microm section by recognizing the characteristic urate crystals in 48% and 38% of the cases, respectively. CONCLUSIONS: This inexpensive adjunctive tool can be used to document gout crystals in almost half of skin biopsies. PMID- 19476525 TI - Extra-abdominal subcutaneous metastasis of a gastrointestinal stromal tumor: report of a case and a review of the literature. AB - Gastrointestinal stromal tumors (GISTs) metastasize primarily within the peritoneal cavity and to the liver. Superficial soft tissue metastases occur in about 1% of advanced GIST and are mostly associated with abdominal laparotomy scars and advanced disease. Extra-abdominal subcutaneous metastases of GIST have not been previously reported. Subcutaneous spindle cell tumors constitute a diagnostic challenge of which the differential diagnostic list can be limited by recognition of morphological, immunohistochemical en molecular genetic patterns. A 69-year-old woman presented with a fast growing subcutaneous nodule on her right upper arm. She was known with an imatinib-resistant advanced GIST, treated with sunitinib. The nodule was excised. Histopathological examination revealed a sharply demarcated tumor nodule in the subcutaneous fat with slightly spindled tumor cells, with pleomorphic nuclei and multiple mitoses. There was a hemangiopericytomatous vascular pattern. The cells stained positive for CD117 (KIT) and CD34. No KIT or platelet-derived growth factor receptor-alpha mutations were detected. We report the first case of an extra-abdominal subcutaneous metastasis of GIST. Although rare, metastatic GIST should therefore be included in the differential diagnosis of subcutaneous spindle cell tumors. A comparative survey of the histological, immunohistochemical and molecular genetic features of spindle cell tumors of the subcutis and a review of the literature is presented. PMID- 19476526 TI - Epithelial sheath neuroma: be aware of benign perineural invasion! AB - Perineural involvement by epithelial cells is usually considered as a sign of malignancy and is seen in a variety of malignant skin neoplasms. However, there are other benign conditions characterized by the presence of perineural involvement by epithelial cells. We present a case of epithelial sheath neuroma in a 43-year-old male. The clinicopathological features of this newly described entity are discussed together with the differential diagnosis and the different hypotheses of pathogenesis. Both pathologists and dermatologists should be aware of this entity to avoid misdiagnosis of malignancy. PMID- 19476527 TI - Clear (pale) cell acanthosis as an incidental finding. AB - Different patterns of epidermal change, including epidermolytic hyperkeratosis and acantholytic dyskeratosis, may represent the predominant histopathologic finding in several localized and generalized processes. Occasionally, minute foci of these reaction patterns are identified as an incidental finding in a biopsy taken because of the presence of some other lesion. Clear (pale) cell acanthosis may occur as the main histologic alteration in clear (pale) cell acanthoma or incidentally, such as may be seen within a seborrheic keratosis. Two cases of incidental minute foci of clear (pale) cell acanthosis are described and put into the broader context of other epidermal histologic reaction patterns. PMID- 19476529 TI - Apocrine hidradenocarcinoma showing Paget's disease and mucinous metaplasia. AB - A 54-year-old man presented with a solitary, erythematous, rapidly growing 1-cm nodule on his scalp that had arisen over the previous 3 months. He had no history of skin cancer. An excisional biopsy of the lesion showed a fairly well circumscribed but focally invasive tumor consisting of areas of typical-appearing clear cell hidradenoma as well as areas with mucinous goblet-type cells and cells with eosinophilic cytoplasm and decapitation-type secretion. There was marked cellular atypia, numerous atypical mitotic figures and focal necrosis. The tumor cells focally involved the overlying epidermis (Paget's disease). Large areas of mucin were identified throughout the lesion. The tumor cells stained with markers for cytokeratin 7 and focally for EMA and CEA, confirming ductal differentiation. The goblet cells and mucinous areas stained with mucicarmine and PASD. The patient was diagnosed with hidradenocarcinoma with mucinous differentiation. Associated Paget's disease has only rarely been reported, and mucinous metaplasia is a previously unreported feature in hidradenocarcinoma. PMID- 19476528 TI - Foreign-body-associated granulomatous slack skin in folliculotropic mycosis fungoides of childhood. AB - Presented in part at the XXVIII Symposium of the International Society of Dermatopathology, Paris, November 14-17, 2007. A 13-year-old boy developed a bulky mass close to the right axillary region and an infiltrated plaque on the abdominal skin. Two years earlier, the diagnosis of follicular mycosis fungoides has been established. Biopsies of both areas revealed typical features of granulomatous slack skin (GSS). Within some of the giant cells, doubly refractile material of unknown origin was found. It may be speculated that in the reported case of follicular mycosis fungoides in childhood, GSS developed as a specific reaction pattern of the disease because of foreign bodies. PMID- 19476531 TI - Plaque-like osteoma cutis with transepidermal elimination. AB - Osteoma cutis is a rare lesion that consists of the presence of bone tissue within the dermis and/or hypodermis. It may be classified as primary osteoma cutis, when bone tissue develops in the skin without any pre-existing lesion and secondary osteoma cutis, which is more frequent and occurs when osseous tissue develops on a pre-existing lesion. We present a case of primary plaque-like osteoma cutis involving the scalp, left forehead and left cheek, which appeared in an adult male. Histopathological study showed several islands of mature osseous tissue involving the full thickness of the dermis. In some areas, there was also transepidermal elimination of bone spicules. We review the literature about previously reported similar cases. PMID- 19476530 TI - Non-sentinel lymph node involvement in a patient with an atypical Spitz tumor and a positive sentinel node. Report of a case and review of the literature. AB - We report a 20-year-old male patient with an atypical Spitz tumor, located in the dorsal aspect of his left hand, and a positive sentinel axillary lymph node. After lymphadenectomy, 1 of 23 non-sentinel lymph nodes excised was found to contain small multiple deposits of large spindle atypical melanocytes. Reviewing the pertinent literature, 5 of 29 patients with atypical Spitz tumors and positive sentinel nodes who had undergone lymphadenectomy have shown non-sentinel node involvement (17.2%), a proportion similar to that reported in melanoma patients. The exact nature of atypical Spitz tumors and the interpretation of cell deposits detected in sentinel nodes are still debated; data regarding the non-sentinel lymph node involvement in patients with atypical Spitz tumors may contribute to better understand the real biological potential of such tumors. PMID- 19476532 TI - Neural fibrolipoma without macrodactyly: a subcutaneous rare benign tumor. AB - Neural fibrolipoma, also known as lipofibromatous hamartoma of nerves and neurolipomatosis, is a rare subcutaneous benign lesion involving the upper extremity with a marked predilection for median nerve. In one-third of the cases, it is associated with macrodactyly (enlargement of one or several digits of hands or feet), diminished sensation, paraesthesias and compression neuropathy. A 23 year-old male presented with a gradually increasing mass in the right palm without associated macrodactyly or neurodeficit. The surgical specimen showed a 20 x 18 x 3 cm, grey yellow fusiform mass. Cut section revealed presence of fibrofatty tissue within and around the enlarged nerve. Microscopy established the relation of nerve enlargement to infiltration of epineurium and perineurium by fibroadipose tissue separating normal nerve fascicles. Limited excision was the mainstay of conservative treatment. Neural fibrolipomas are a rare entity. Knowledge of characteristic histological and radiological findings is necessary for diagnosis and treatment. PMID- 19476533 TI - Folliculosebaceous cystic hamartoma of the nipple: a case report. AB - Folliculosebaceous cystic hamartoma (FCH) is a relatively rare and recently described lesion of the skin. Mostly, it involves the skin of the head and neck area. It is considered by most authors as a form of non-neoplastic cutaneous hamartoma comprising follicular, sebaceous and stromal elements. However, few regard it as a sebaceous trichofolliculoma, i.e. a variant of trichofolliculoma. FCH of the nipple of female breast is a very rare lesion with only one previous case reported so far in the literature. We report a similar case with a brief review of the literature. PMID- 19476534 TI - Papillary hemangioma on the face. PMID- 19476538 TI - To our readers. PMID- 19476535 TI - Nevoid basal cell carcinoma syndrome versus generalized basaloid follicular hamartoma syndrome. PMID- 19476539 TI - Dicer and micro-RNAs in cutaneous disease. PMID- 19476540 TI - Gene expression profiling to define host response to baculoviral transduction in the brain. AB - Recombinant baculoviral vectors efficiently transduce several types of cells in the brain. To characterize host responses to virus challenge, thus verifying the suitability of using baculovirus for the development of gene therapy strategies in the central nervous system, we used cDNA microarray technology to examine in vitro and in vivo global cellular gene expression profiles in the rat brain, cultured human astrocytes and human neuronal cells after viral transduction. We demonstrated that the transduction induced host antiviral responses as a major reaction in all three types of samples profiled. The related genes were mainly those associated with innate immunity, including several of the genes involved in Toll-like receptor signaling pathway and cytokine-cytokine receptor interaction. These findings should be useful in understanding the molecular basis for neural cell response to baculoviral transduction and in guiding rational therapeutic applications of baculoviral vectors in the central nervous systems. PMID- 19476541 TI - Cellular calcium deficiency plays a role in neuronal death caused by proteasome inhibitors. AB - Cytosolic Ca(2+) concentration ([Ca(2+)](i)) is reduced in cultured neurons undergoing neuronal death caused by inhibitors of the ubiquitin proteasome system. Activation of calcium entry via voltage-gated Ca(2+) channels restores cytosolic Ca(2+) levels and reduces this neuronal death (Snider et al. 2002). We now show that this reduction in [Ca(2+)](i) is transient and occurs early in the cell death process, before activation of caspase 3. Agents that increase Ca(2+) influx such as activation of voltage-gated Ca(2+) channels or stimulation of Ca(2+) entry via the plasma membrane Na-Ca exchanger attenuate neuronal death only if applied early in the cell death process. Cultures treated with proteasome inhibitors had reduced current density for voltage-gated Ca(2+) channels and a less robust increase in [Ca(2+)](i) after depolarization. Levels of endoplasmic reticulum Ca(2+) were reduced and capacitative Ca(2+) entry was impaired early in the cell death process. Mitochondrial Ca(2+) was slightly increased. Preventing the transfer of Ca(2+) from mitochondria to cytosol increased neuronal vulnerability to this death while blockade of mitochondrial Ca(2+) uptake via the uniporter had no effect. Programmed cell death induced by proteasome inhibition may be caused in part by an early reduction in cytosolic and endoplasmic reticulum Ca(2+,) possibly mediated by dysfunction of voltage-gated Ca(2+) channels. These findings may have implications for the treatment of disorders associated with protein misfolding in which proteasome impairment and programmed cell death may occur. PMID- 19476542 TI - Tumor necrosis factor-alpha-induced neutral sphingomyelinase-2 modulates synaptic plasticity by controlling the membrane insertion of NMDA receptors. AB - The insertion and removal of NMDA receptors from the synapse are critical events that modulate synaptic plasticity. While a great deal of progress has been made on understanding the mechanisms that modulate trafficking of NMDA receptors, we do not currently understand the molecular events required for the fusion of receptor containing vesicles with the plasma membrane. Here, we show that sphingomyelin phosphodiesterase 3 (also known as neutral sphingomyelinase-2) is critical for tumor necrosis factor (TNF) alpha-induced trafficking of NMDA receptors and synaptic plasticity. TNFalpha initiated a rapid increase in ceramide that was associated with increased surface localization of NMDA receptor NR1 subunits and a specific clustering of NR1 phosphorylated on serines 896 and 897 into lipid rafts. Brief applications of TNFalpha increased the rate and amplitude of NMDA-evoked calcium bursts and enhanced excitatory post-synaptic currents. Pharmacological inhibition or genetic mutation of neutral sphingomyelinase-2 prevented TNFalpha-induced generation of ceramide, phosphorylation of NR1 subunits, clustering of NR1, enhancement of NMDA-evoked calcium flux and excitatory post-synaptic currents. PMID- 19476544 TI - Toxic effect of blood components on perinatal rat subventricular zone cells and oligodendrocyte precursor cell proliferation, differentiation and migration in culture. AB - The germinal matrix of human brain gives rise to oligodendrocytes and astrocytes after mid-gestation. Hemorrhage in the germinal matrix of premature infants is associated with suppressed cell proliferation. We hypothesize that soluble blood constituents have an adverse effect on the proliferation of cultured rat subventricular zone (SVZ) cells and the proliferation, migration, and differentiation of oligodendrocyte progenitor cells (OPC). Using caspase 3 activation and lactate dehydrogenase release assays, rat plasma, serum, thrombin, and kallikrein killed SVZ cells when grown in the presence (but not absence) of platelet derived growth factor. Plasma and serum killed OPC at 1:1 to 1:100 dilutions. Using a bromodeoxyuridine incorporation assay OPC proliferation was reduced by plasma, serum, thrombin and plasmin. Blood proteins also suppressed OPC migration in a concentration dependent manner. However, differentiation of OPC into myelin basic protein expressing cells was suppressed only by thrombin. We conclude that soluble blood components, particularly thrombin, have an adverse effect on maturing SVZ cells and OPC derived from newborn rat brain. PMID- 19476545 TI - Amyloid precursor protein promotes endoplasmic reticulum stress-induced cell death via C/EBP homologous protein-mediated pathway. AB - The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) is known to activate the ER, which is termed ER stress. Here, we demonstrated that amyloid precursor protein (APP) is a novel mediator of ER stress-induced apoptosis through the C/EBP homologous protein (CHOP) pathway. Expression of APP mRNA was elevated by tunicamycin- or dithiothreitol-induced ER stress. The levels of C83 and APP intracellular domain (AICD) fragments, which are cleaved from APP, were significantly increased under ER stress, although the protein level of full-length APP was decreased. Cellular viability was reduced in APP-over-expressing cells, which was attenuated by treatment with a gamma secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t butyl ester (DAPT). Cellular viability was also reduced in AICD-FLAG-over expressing cells. The mRNA and protein levels of CHOP, an ER stress-responsive gene, were remarkably increased by APP over-expression, which was attenuated by treatment with DAPT. CHOP mRNA induction was also found in AICD-FLAG-over expressing cells. Cell death and CHOP up-regulation by ER stress were attenuated by APP knockdown. Data obtained with a luciferase assay and chromatin immunoprecipitation assay indicated that AICD associates with the promoter region of the CHOP gene. In conclusion, ER stress-induced APP undergoes alpha- and gamma secretase cleavage and subsequently induces CHOP-mediated cell death. PMID- 19476543 TI - Induction of tyrosine hydroxylase mRNA by nicotine in rat midbrain is inhibited by mifepristone. AB - Repeated nicotine administration induces tyrosine hydroxylase (TH) mRNA in rat midbrain. In this study we investigate the mechanisms responsible for this response using two models of midbrain dopamine neurons, rat ventral midbrain slice explant cultures and mouse MN9D cells. In both models nicotine stimulates TH gene transcription rate in a dose-dependent manner. However, this stimulation is short-lived, lasting for 1 h, but less than 3 h, and is not sufficient to induce TH mRNA or TH protein. Nicotine elevates circulating glucocorticoids, which induce TH expression in some model systems. We tested the hypothesis that the effect of nicotine on midbrain TH mRNA is mediated by the glucocorticoid receptor. When rats are administered the glucocorticoid receptor antagonist mifepristone, the induction of TH mRNA by nicotine in both substantia nigra and ventral tegmentum is inhibited. Furthermore, the glucocorticoid receptor agonist dexamethasone stimulates TH gene transcription for sustained periods of time in both midbrain slices and MN9D cells, leading to induction of TH mRNA and TH protein. Our results are consistent with the hypothesis that nicotine induces TH mRNA in midbrain by elevating glucocorticoids, which then act on glucocorticoid receptors in dopamine neurons leading to transcriptional activation of the TH gene. PMID- 19476546 TI - Ginsenoside Rg1 protects against 6-OHDA-induced neurotoxicity in neuroblastoma SK N-SH cells via IGF-I receptor and estrogen receptor pathways. AB - Our previous studies have demonstrated that ginsenoside Rg1 is a novel class of potent phytoestrogen and can mimic the action of estradiol in stimulation of MCF 7 cell growth by the crosstalk between insulin-like growth factor-I receptor (IGF IR)-dependent pathway and estrogen receptor (ER)-dependent pathway. The present study was designed to investigate the neuroprotective effects of ginsenoside Rg1 against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human neuroblastoma SK-N-SH cells and the possible mechanisms. Pre-treatment with ginsenoside Rg1 resulted in an enhancement of survival, and significant rescue occurred at the concentration of 0.01 microM on cell viability against 6-OHDA-induced neurotoxicity. These effects could be completely blocked by IGF-IR antagonist JB 1 or ER antagonist ICI 182780. 6-OHDA arrested the cells at G(0)G(1) phase and prevented S phase entry. Rg1 pre-treatment could reverse the cytostatic effect of 6-OHDA. Ginsenoside Rg1 also could attenuate 6-OHDA-induced decrease in mitochondrial membrane potential. These effects could also be completely blocked by JB-1 or ICI 182780. Furthermore, 6-OHDA-induced up-regulation of Bax and down regulation of Bcl-2 mRNA and protein expression could be restored by Rg1 pre treatment. Rg1 pre-treatment could reverse the down-regulation of ER alpha protein expression induced by 6-OHDA treatment. Cells transfected with the estrogen responsive element (ERE)-luciferase reporter construct exhibited significantly increased ERE-luciferase activity in the Rg1 presence, suggesting that the estrogenic effects of Rg1 were mediated through the endogenous ERs. These results suggest that ginsenoside Rg1 may attenuate 6-OHDA-induced apoptosis and its action might involve the activation of IGF-IR signaling pathway and ER signaling pathway. PMID- 19476547 TI - Inducible over-expression of wild type alpha-synuclein in human neuronal cells leads to caspase-dependent non-apoptotic death. AB - Alpha-synuclein (ASYN) is central in Parkinson's disease pathogenesis. Converging pieces of evidence suggest that the levels of ASYN expression play a critical role in both familial and sporadic Parkinson's disease. To elucidate the mechanism underlying wild type (WT) ASYN-mediated neurotoxicity, we have generated a novel Tet-Off SHSY-5Y cell line, conditionally expressing WT ASYN. Induction of human WT ASYN in retinoic acid-differentiated SHSY-5Y cells leads to accumulation of soluble ASYN oligomers, in the absence of inclusions, and to gradual cellular degeneration. Morphologically, the death observed is non apoptotic. Caspases other than caspase 3, including caspase 9, are activated and caspase inhibition diminishes death by acting at a point upstream of cytochrome c release. Application of Scyllo-inositol, an oligomer-stabilizing compound, prevents neuronal death in this model. These findings are consistent with a model in which oligomeric ASYN triggers the initial activation of the apoptotic pathway, which is however blocked downstream of the mitochondrial checkpoint, thus leading to a death combining in a unique fashion both apoptotic and non apoptotic features. This novel inducible cell model system may prove valuable in the deciphering of WT ASYN-induced pathogenic effects and in the assessment and screening of potential therapeutic strategies. PMID- 19476548 TI - The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration. AB - The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography, and related this to 5 HT transporter (S)-[N-methyl-(3)H]citalopram binding. We also determined the regulation of 5-HT(4) receptor binding by 1, 14, and 21 days of paroxetine administration and subchronic 5-HT depletion, and compared this with changes in 5 HT(2A) receptor [(3)H]MDL100907 binding. In the Flinders Sensitive Line, the 5 HT(4) receptor and 5-HT transporter binding were decreased in the dorsal and ventral hippocampus, and the changes in binding were directly correlated within the dorsal hippocampus. Chronic but not acute paroxetine administration caused a 16-47% down-regulation of 5-HT(4) receptor binding in all regions evaluated including the basal ganglia and hippocampus, while 5-HT depletion increased the 5 HT(4) receptor binding in the dorsal hippocampus, hypothalamus, and lateral globus pallidus. In comparison, the 5-HT(2A) receptor binding was decreased in the frontal and cingulate cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT(4) receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration. PMID- 19476549 TI - Dynamic chromatin remodeling events in hippocampal neurons are associated with NMDA receptor-mediated activation of Bdnf gene promoter 1. AB - To determine the epigenetic events associated with NMDA receptor-mediated activation of brain-derived neurotrophic factor gene (Bdnf) promoter 1 by hippocampal neurons in culture, we screened 12 loci across 4.5 kb of genomic DNA 5' of the transcription start site (TSS) of rat Bdnf for specific changes in histone modification and transcription factor binding following NMDA receptor stimulation. Chromatin immunoprecipitation (ChIP) assays showed that NMDA receptor stimulation produced a durable, time-dependent decrease in histone H3 at lysine 9 dimethylation (H3K9me2), within 3 h after NMDA treatment across multiple loci. Concomitant increases in H3K4me2 and H3K9/14 acetylation (H3AcK9/14) were associated with transcriptional activation, but occurred at fewer sites within the promoter. The decrease in H3K9me2 was associated with release of HDAC1, MBD1, MeCP2, and REST from specific locations within promoter 1, although with different kinetics. In addition, occupancy of sites proximal to and distal to the TSS by the transcription factors NF-kappaB, CREB-binding protein (CBP), and cAMP response element-binding protein were correlated with increased occupancy of RNA polymerase II at two loci proximal to the TSS following NMDA receptor stimulation. These temporal changes in promoter occupancy could occur thousands of base pairs 5' of the TSS, suggesting a mechanism that produces waves of Bdnf transcription. PMID- 19476550 TI - Chronic stress elicits prolonged activation of alpha-MSH secretion and subsequent degeneration of melanotroph. AB - Prolonged stress affects homeostasis in various organs and induces stress associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up-regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of alpha-melanocyte stimulating hormone (alpha-MSH), a major product of proopiomelanocortin in IL were increased. The alpha-MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus derived dopamine release in IL, which elicited over-secretion of alpha-MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration. PMID- 19476551 TI - Fibroblast growth factor 9 prevents MPP+-induced death of dopaminergic neurons and is involved in melatonin neuroprotection in vivo and in vitro. AB - Oxidative stress and down-regulated trophic factors are involved in the pathogenesis of nigrostriatal dopamine(DA)rgic neurodegeneration in Parkinson's disease. Fibroblast growth factor 9 (FGF9) is a survival factor for various cell types; however, the effect of FGF9 on DA neurons has not been studied. The antioxidant melatonin protects DA neurons against neurotoxicity. We used MPP(+) to induce neuron death in vivo and in vitro and investigated the involvement of FGF9 in MPP(+) intoxication and melatonin protection. We found that MPP(+) in a dose- and time-dependent manner inhibited FGF9 mRNA and protein expression, and caused death in primary cortical neurons. Treating neurons in the substantia nigra and mesencephalic cell cultures with FGF9 protein inhibited the MPP(+) induced cell death of DA neurons. Melatonin co-treatment attenuated MPP(+) induced FGF9 down-regulation and DA neuronal apoptosis in vivo and in vitro. Co treating DA neurons with melatonin and FGF9-neutralizing antibody prevented the protective effect of melatonin. In the absence of MPP(+), the treatment of FGF9 neutralizing antibody-induced DA neuronal apoptosis whereas FGF9 protein reduced it indicating that endogenous FGF9 is a survival factor for DA neurons. We conclude that MPP(+) down-regulates FGF9 expression to cause DA neuron death and that the prevention of FGF9 down-regulation is involved in melatonin-provided neuroprotection. PMID- 19476552 TI - Modulation of stress proteins and apoptotic regulators in the anoxia tolerant turtle brain. AB - Freshwater turtles survive prolonged anoxia and reoxygenation without overt brain damage by well-described physiological processes, but little work has been done to investigate the molecular changes associated with anoxic survival. We examined stress proteins and apoptotic regulators in the turtle during early (1 h) and long-term anoxia (4, 24 h) and reoxygenation. Western blot analyses showed changes within the first hour of anoxia; multiple stress proteins (Hsp72, Grp94, Hsp60, Hsp27, and HO-1) increased while apoptotic regulators (Bcl-2 and Bax) decreased. Levels of the ER stress protein Grp78 were unchanged. Stress proteins remained elevated in long-term anoxia while the Bcl-2/Bax ratio was unaltered. No changes in cleaved caspase 3 levels were observed during anoxia while apoptosis inducing factor increased significantly. Furthermore, we found no evidence for the anoxic translocation of Bax from the cytosol to mitochondria, nor movement of apoptosis inducing factor between the mitochondria and nucleus. Reoxygenation did not lead to further increases in stress proteins or apoptotic regulators except for HO-1. The apparent protection against cell damage was corroborated with immunohistochemistry, which indicated no overt damage in the turtle brain subjected to anoxia and reoxygenation. The results suggest that molecular adaptations enhance pro-survival mechanisms and suppress apoptotic pathways to confer anoxia tolerance in freshwater turtles. PMID- 19476555 TI - Genetic analysis of aquabirnaviruses isolated from wild fish reveals occurrence of natural reassortment of infectious pancreatic necrosis virus. AB - In this study, we report the sequencing of the whole genome [including the 5' and 3' non-coding regions (NCR) of both segments A and B] of seven birnavirus strains isolated from wild fish from the Flemish Cap (FC) fishery at Newfoundland, Canada. From analysis and comparison of the sequences, most of the FC isolates clustered with the North American reference strains West Buxton (WB), Dry Mill and Jasper. One strain was included in the same genotype as the European strain Ab. In addition, at least in one case cohabitation of both type strains in an individual fish was demonstrated. These results clearly suggest the acquisition of the viruses from two different sources. The prevalence of the American type is easily explained by the close proximity of this fishing bank to the American coast whereas, although surprising, the presence of the European type strain could be because of migration of fish from European waters. In one strain, segment A and B sequences were typed differently (WB and Ab, respectively). These findings indicate natural reassortment between two strains of aquabirnaviruses in a host. PMID- 19476556 TI - Sensitivity of autologous serum skin test for chronic autoimmune urticaria. PMID- 19476557 TI - A simple non-enzymatic method for the preparation of white spot syndrome virus (WSSV) DNA from the haemolymph of Marsupenaeus japonicus using FTA matrix cards. AB - White spot syndrome virus (WSSV) is an important shrimp pathogen responsible for large economic losses for the shrimp culture industry worldwide. The nucleic acids of the virus must be adequately preserved and transported from the field to the laboratory before molecular diagnostic analysis is performed. Here, we developed a new method to isolate WSSV-DNA using Flinders Technology Associates filter paper (FTA matrix card; Whatman) without centrifugation or hazardous steps involved. FTA technology is a new method allowing the simple collection, shipment and archiving of nucleic acids from haemolymph samples providing DNA protection against nucleases, oxidation, UV damage, microbial and fungal attack. DNA samples prepared from 10-fold dilutions of moribund shrimp haemolymph using FTA matrix cards were analysed using semi-quantitative and quantitative polymerase chain reaction (PCR) and were compared with two commercially available DNA isolation methods, the blood GenomicPrep Mini Spin Kit (GE Healthcare) and the DNAzol (Invitrogen). Sequence analysis was performed for the DNA samples prepared using the various isolation procedures and no differences in the sequence among these methods were identified. Results based on the initial copy number of DNA prepared from the GenomicPrep Mini Spin Kit are a little more sensitive than the DNA prepared from FTA matrix cards, whereas the DNAzol method is not suitable for blood samples. Our data shows the efficiency of retention capacity of WSSV-DNA samples from impregnated FTA matrix cards. Matrix cards were easy to store and ship for long periods of time. They provide ease of handling and are a reliable alternative for sample collection and for molecular detection and characterization of WSSV isolates. PMID- 19476558 TI - Pseudomonas chlororaphis strain JF3835 reduces mortality of juvenile perch, Perca fluviatilis L., caused by Aeromonas sobria. AB - Motile aeromonad septicaemia caused by Aeromonas sobria is a cause of disease in farmed perch, Perca fluviatilis L., in Switzerland. We have evaluated the potential of a Pseudomonas chlororaphis isolate, obtained from perch intestine, to control A. sobria infection. Inoculation of juvenile perch with P. chlororaphis strain JF3835 prior to infection with A. sobria caused a reduction in A. sobria associated mortalities. Infection of perch with xylE-labelled P. chlororaphis indicated the bacterium is able to transiently colonize juvenile fish and fingerlings. PMID- 19476553 TI - Combination therapy with coenzyme Q10 and creatine produces additive neuroprotective effects in models of Parkinson's and Huntington's diseases. AB - Coenzyme Q(10) (CoQ(10)) and creatine are promising agents for neuroprotection in neurodegenerative diseases via their effects on improving mitochondrial function and cellular bioenergetics and their properties as antioxidants. We examined whether a combination of CoQ(10) with creatine can exert additive neuroprotective effects in a MPTP mouse model of Parkinson's disease, a 3-NP rat model of Huntington's disease (HD) and the R6/2 transgenic mouse model of HD. The combination of the two agents produced additive neuroprotective effects against dopamine depletion in the striatum and loss of tyrosine hydroxylase neurons in the substantia nigra pars compacta (SNpc) following chronic subcutaneous administration of MPTP. The combination treatment resulted in significant reduction in lipid peroxidation and pathologic alpha-synuclein accumulation in the SNpc neurons of the MPTP-treated mice. We also observed additive neuroprotective effects in reducing striatal lesion volumes produced by chronic subcutaneous administration of 3-NP to rats. The combination treatment showed significant effects on blocking 3-NP-induced impairment of glutathione homeostasis and reducing lipid peroxidation and DNA oxidative damage in the striatum. Lastly, the combination of CoQ(10) and creatine produced additive neuroprotective effects on improving motor performance and extending survival in the transgenic R6/2 HD mice. These findings suggest that combination therapy using CoQ(10) and creatine may be useful in the treatment of neurodegenerative diseases such as Parkinson's disease and HD. PMID- 19476559 TI - Virus-like particles associated with brown muscle disease in Manila clam, Ruditapes philippinarum, in Arcachon Bay (France). AB - Recently, Manila clam, Ruditapes philippinarum, populations have suffered mortalities in Arcachon Bay (SW France). Mortality was associated with extensive lesions of the posterior adductor muscle, which become progressively brown and calcified. Ultrastructural observations by transmission electron microscopy revealed tissue degradation with necrotized muscle fibres and granulocytomas. Unenveloped virus-like particles (VLPs) were detected in muscle, granulocytic, epithelial and rectal cells. VLPs were abundant in the extracellular space, in the cytoplasm (free or enclosed in vesicles) and in the nucleoplasm of granulocytes. Nuclei and mitochondria of granulocytes displayed changes which suggested reactive oxygen species production and apoptosis induction. VLPs exhibited an icosahedral structure with a diameter of 25 to 35 nm. These observations suggest that the VLPs could belong to the family Picornaviridae or the Parvoviridae. PMID- 19476561 TI - Gastroscopy in immigrants of Turkish descent. AB - BACKGROUND AND AIM: Little data is known on morbidity and Helicobacter pylori in the upper part of the gastrointestinal tract in male and female patients of Turkish descent. A study was done in order to assess the presence of H. pylori in Turkish men and women in relation to the diagnostic yield of the endoscopy. METHODS: All consecutive patients of Turkish descent were included in the present study. Detection of H. pylori was done with hematoxylin-eosin stain, an immunoperoxidase and Gram stain and culture. RESULTS: In 16 years, 2427 procedures (10.4%) were done in Turkish patients. After exclusions, 842 endoscopies in Turkish women and 827 procedures in Turkish men remained. Peptic ulcer disease was diagnosed in 101 (6%) patients and reflux esophagitis in 97 patients (5.8%). Seven patients had cancer. In 749 patients (64%), no macroscopic abnormalities were seen. Turkish men suffered more often from reflux esophagitis (81% vs 19%, P < 0.0001), hiatus hernia (58% vs 42%, P < 0.0001) and peptic ulcer disease (74% vs 26%, P < 0.0001). Women more often showed no abnormalities (P < 0.0001). There was no change in the yearly prevalence of reflux esophagitis and peptic ulcer disease in women, while the peptic ulcers decreased, and reflux esophagitis increased in men. Men were significantly more often H. pylori positive (P = 0.03). There was a clear trend towards a decrease in H. pylori positives. CONCLUSION: There are differences in the presence of ulcer disease and reflux esophagitis between Turkish men and women. Men are significantly more often H. pylori-positive. Prevalence of H. pylori infection in Turkish patients slowly decreases in the consecutive years in both men and women. PMID- 19476560 TI - Prevalence and risk factors for non-alcoholic fatty liver disease among adults in an urban Sri Lankan population. AB - BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in the Asia-Pacific region. However, its prevalence and risk factors in Asian (especially South Asian) communities is poorly studied. In this study, the aim was to determine the community prevalence and risk factors for NAFLD among adults in an urban Sri Lankan population. METHODS: The study population consisted of 35-64-year-old adults, selected by stratified random sampling. NAFLD was diagnosed on established ultrasound criteria for fatty liver, safe alcohol consumption (< 14 units/week for men, < 7 units/week for females) and absence of hepatitis B and C markers. Blood pressure (BP) and anthropometric measurements were made, and fasting glucose, glycosylated hemoglobin, serum lipids, fasting serum insulin and serum alanine aminotransferase (ALT) were determined. RESULTS: Of the 2985 study participants, 974 (32.6%) had NAFLD (605 [62.1%] women, mean age 52.8 years [standard deviation, 7.3]). On multivariate analysis, obesity, acanthosis nigricans, insulin resistance, elevated diastolic BP, fasting plasma glucose, plasma triglycerides, and ALT twice the upper limit of the reference range or more were independently associated with NAFLD. CONCLUSION: The prevalence of NAFLD among adults in this urban Sri Lankan community is high and is strongly associated with constituent features of the metabolic syndrome. PMID- 19476562 TI - Resistance to metronidazole, clarithromycin and levofloxacin of Helicobacter pylori before and after clarithromycin-based therapy in Taiwan. AB - BACKGROUND AND AIM: Clarithromycin-based triple therapy has been commonly applied as the first-line therapy for Helicobacter pylori eradication. Levofloxacin could serve as an alternative in either first-line or second-line regimens. This study surveyed the prevalence of levofloxacin resistance of H. pylori isolates in naive patients and in patients with a failed clarithromycin-based triple therapy. METHODS: The study collected the H. pylori isolates from 180 naive patients and 47 patients with a failed clarithromycin-based triple therapy. Their in vitro antimicrobial resistance was determined by E-test. RESULTS: The naive H. pylori isolates had resistance rates for amoxicillin, levofloxacin, clarithromycin and metronidazole of 0%, 9.4%, 10.6% and 26.7%, respectively. An evolutional increase of the primary levofloxacin resistance was observed in isolates collected after 2004, as compared to isolates collected before 2004 (16.3% vs 3.2%, P = 0.003). There was no evolutional increment of the primary clarithromycin resistance. The clarithromycin resistance elevated significantly after a failed clarithromycin based triple therapy (78.7% vs 10.6%, P < 0.001). The post-treatment isolates remained to have a levofloxacin resistance rate of near 17%, but the levofloxacin resistant isolates were correlated with a higher incidence of metronidazole resistance (P = 0.023). No strain was found to be resistant to amoxicillin even after eradication failure. CONCLUSION: The levofloxacin resistance of naive H. pylori remains less than 10% in Taiwan. With relatively lower resistance to levofloxacin than to metronidazole of the H. pylori isolates collected after a failed clarithromycin-based therapy, proton pump inhibitor-levofloxacin amoxicillin may be an alternative choice to serve as the second-line therapy. PMID- 19476563 TI - Clinical fate of branch duct and mixed forms of intraductal papillary mucinous neoplasia of the pancreas. AB - AIMS: The aim of the present study was to assess the clinical fate of, and to gain new insights into, branch duct and mixed (predominantly main duct type) forms of intraductal papillary mucinous neoplasia of the pancreas (IPMN). METHODS: During a 17-year period, 99 successive IPMN patients (52 men, 47 women; mean age, 64 years) were included and divided into two groups for further comparison: one group had branch duct IPMN, whereas the other had mixed IPMN. RESULTS: Patients from the mixed IPMN group (n = 52) displayed a greater rate of symptoms (83% vs 55%, P = 0.004), pancreatic resection (67% vs 38%, P = 0.007), malignancy (35% vs 13%, P = 0.017) and death (15% vs 4%, P = 0.09) than those from the branch duct IPMN group. A 38-month follow up of non-operated, symptom free patients confirmed that more than 85% of branch duct IPMN patients were asymptomatic without evidence of malignancy. Borderline lesions and carcinoma are found in up to 50% of symptomatic resected branch duct IPMN cases. CONCLUSION: Patients with the mixed form of IPMN as well as with symptomatic branch duct IPMN should require pancreatic resection because of symptoms and the risk for malignancy. In silent branch duct IPMN without radiological signs of malignancy, a non-operative watch-and-wait strategy can be discussed. PMID- 19476564 TI - Development and evaluation of a vaginal ring device for sustained delivery of HIV microbicides to non-human primates. AB - BACKGROUND: There is considerable interest in developing coitally independent, sustained release formulations for long-term administration of HIV microbicides. Vaginal ring devices are at the forefront of this formulation strategy. METHODS: Non-medicated silicone elastomer vaginal rings were prepared having a range of appropriate dimensions for testing vaginal fit in pig-tailed and Chinese rhesus macaques. Cervicovaginal proinflammatory markers were evaluated. Compression testing was performed to compare the relative flexibility of various macaque and commercial human rings. RESULTS: All rings remained in place during the study period and no tissue irritation or significant induction of cervicovaginal proinflammatory markers or signs of physical discomfort were observed during the 8-week study period. CONCLUSIONS: Qualitative evaluation suggests that the 25 x 5 mm ring provided optimal fit in both macaque species. Based on the results presented here, low-consistency silicone elastomers do not cause irritation in macaques and are proposed as suitable materials for the manufacture of microbicide-loaded vaginal rings. PMID- 19476565 TI - A case of WHIM syndrome associated with diabetes and hypothyroidism. AB - The WHIM syndrome is a rare immunological disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. We hypothesized that immunological or genetic mechanisms may link WHIM syndrome and type 1 diabetes. We report that the young girl with WHIM syndrome developed diabetes and transient hypothyroidism. A nonsense mutation (C-->T) truncating the CXC chemokine receptor 4 (CXCR4) C-terminal cytoplasmic tail domain occurred at nucleotide position 1000(R334X) of the CXCR4 gene in one allele of the patient was identified, and the person was diagnosed as having WHIM syndrome. Recent observation suggested that the CXCR4, a G-protein-coupled receptor with a unique ligand, CXCL12, might be involved in the pathogenesis for type 1 diabetes. Taken into consideration the concurrent prevalence of the two disorders and the speculated common pathogenesis associated with the CXCR4, our patient may enable us to understand the genetic damage related to accelerated apoptosis. PMID- 19476566 TI - Long-term effects of diabetes during pregnancy on the offspring. AB - BACKGROUND: Many epidemiological and experimental studies have proven that some adult diseases might have their origin in fetal life. It has been also hypothesized that intra-uterine environment in pregnancy complicated with diabetes might influence the development of obesity, type 2 diabetes, and cardiovascular diseases in the offspring. OBJECTIVES: To assess glucose metabolism, insulin secretion, and prevalence of obesity in the offspring of mothers with pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) and to evaluate the relationship between maternal metabolic control during pregnancy and metabolic disturbances in children. SUBJECTS: Children of mothers with PGDM (n = 43) and GDM (n = 34) were examined at 4-9 yr of age and compared with the control group (n = 108; metabolic parameters available for n = 29). METHODS: The incidence of overweight and obesity, impaired glucose tolerance, and insulin resistance were analyzed based on anthropometric and biochemical measurements. Statistical analysis was performed with statistica package. RESULTS: In children of GDM mothers, body mass index z-score (0.81 +/- 1.01 vs. -0.04 +/- 1.42 PGDM vs. 0.07 +/- 1.28 control group) and insulin resistance indices (homeostasis model assessment index - insulin resistance 1.112 vs. 0.943 PGDM vs. 0.749 control group) were significantly higher than in other groups. Obesity and insulin resistance were also most frequent in GDM group [not significant (NS)]. In addition, we observed the relationship between maternal hemoglobin A1c and mean glycemia in perinatal period and insulin resistance in children. There was not such correlation for the class of maternal diabetes. CONCLUSION: Children born to mothers with gestational diabetes seem to be at risk for obesity and metabolic disturbances. PMID- 19476567 TI - Prevalence of components of the metabolic syndrome in schoolchildren with newly diagnosed type 2 diabetes mellitus. AB - OBJECTIVE: To examine the prevalence of components of the metabolic syndrome (MS) other than hyperglycemia at diagnosis in schoolchildren with type 2 diabetes mellitus (T2DM). DESIGN: The study involved 112 Japanese schoolchildren, 45 males and 67 females aged 12.9 +/- 1.5 yr, who were diagnosed as having T2DM. The body weight, blood pressure and fasting serum triglyceride (TG), and high-density lipoprotein cholesterol cholesterol (HDL-C) levels were also measured at diagnosis. The criteria adopted for the diagnosis of MS were as follows; i.e., TG > or =150 mg/dL, HDL-C <40 mg/dL, systolic blood pressure > or =130 mmHg, and/or diastolic blood pressure > or =85 mmHg. Obesity was defined as percent overweight > or =20.0%. RESULTS: As much as 83.0% of the patients had obesity. The prevalence of increased TG was 33.0% and that of decreased HDL-C was 21.4% among the patients. Elevated blood pressure was identified in 11.6% of the patients. Of the total, 15.2% of the patients had no other components of MS besides hyperglycemia; 49.1% had only one other component, which was obesity in the majority; 17.0% had two other components of MS besides hyperglycemia, which were obesity and elevated TG in the majority; 18.8% of the patients had three or more components of MS besides hyperglycemia. CONCLUSIONS: We found a high prevalence of other components of MS besides hyperglycemia in the patients even at the time of diagnosis. Early detection of other components of MS would appear to be of importance for preventing the development of cardiovascular disease in children with T2DM. PMID- 19476568 TI - Metabolic syndrome in obese adolescents. AB - Childhood and adolescent obesity is highly prevalent and a relevant public health problem in Chile. Metabolic syndrome (MS), which is predictive of future cardiovascular disease and type 2 diabetes, has been associated with childhood obesity and insulin resistance. The aim of this study was to determine the prevalence of MS in a non-consultant obese adolescent population and to assess the underlying factors for the MS in these subjects. The nutritional status was evaluated for 25,102 students from 10 to 18 years of age living in Concepcin and Coronel, Chile. A total of 2,308 adolescents were found to be obese (BMI > or = 95 percentile). Metabolic syndrome was defined as the presence of at least three of the following abnormalities: waist circumference > or = 90th percentile, blood pressure > or= 90th percentile, fasting glycaemia > or = 100 mg/dL, HDL cholesterol < or = 40 mg/dL and triglycerides > or = 110 mg/dL in a representative sample of 461 adolescents. The results obtained indicate that the prevalence of obesity was 9.2% and that MS reached 37.5%. Only 4.1% of the adolescents failed to present any of the risk factors for MS. When compared with the adolescents without MS, the estimated odd ratios (OR) for the presence of the characteristics of MS were all statistically significant, with increased waist circumference reaching an OR of 21.56. A significant difference was found between adolescents with and without MS; the parameters indicated greater insulin resistance for adolescents with MS. In conclusion, MS is highly prevalent among Chilean adolescents with obesity and its prevention beginning in childhood needs to be addressed. PMID- 19476569 TI - Role of potential immune targets in atherosclerosis for vaccine development. PMID- 19476570 TI - Favorable cardiovascular risk factor profile is associated with reduced prevalence of coronary artery calcification and inflammation in asymptomatic nondiabetic white men. AB - Middle-aged individuals with favorable levels of all major cardiovascular risk factors (CVRFs) have much lower age-specific risks for incident cardiovascular disease (CVD). However, the relationship of the absence of CVRFs with subclinical CVD and inflammation is not well described. We classified 440 asymptomatic Brazilian men (aged 46+/-7 years) based on the number of CVRFs (smoking, systolic blood pressure > or =130 mm Hg, low-density lipoprotein cholesterol > or =130 mg/dL, high-density lipoprotein cholesterol <40 mg/dL, triglycerides > or =150 mg/dL, fasting glucose > or =100 mg/dL, and waist circumference >102 cm). Only 7% had no CVRFs, whereas 1, 2, 3, and > or =4 CVRFs were observed in 18%, 24%, 21%, and 29%, respectively. In age-adjusted analysis, each lower CVRF profile was associated with lower odds of prevalent coronary artery calcium (odds ratio, 0.75; P=.002) and elevated white blood cell count (odds ratio, 0.70; P<.001). Our study supports the notion that a favorable CVD profile is associated with less underlying atherosclerosis and inflammation and further highlights the importance of primary prevention of CVRFs. PMID- 19476571 TI - Efficacy of a pharmacist-led cardiovascular risk reduction clinic for diabetic patients with and without mental health conditions. AB - Coexisting mental health conditions (MHCs) attenuate treatment effects in diabetes. A retrospective analysis was performed of a pharmacist-led cardiovascular risk reduction clinic (CRRC) targeting hypertension, diabetes, hyperlipidemia, and tobacco use in patients with at least one CRRC visit between January 2001 and January 2002. The United Kingdom Prospective Diabetes Study (UKPDS) risk change (after/before CRRC) for those with and without MHCs was compared. Of the 297 with diabetes and complete UKPDS data, 40.7% had at least 1 MHC (22.3% had a severe MHC). Patients with MHCs had a similar number of CRRC visits (4.7+/-2.6 vs 4.4+/-2.6) but had a lower baseline UKPDS score (0.31+/-0.18 vs 0.40+/-0.20; P=.001) compared with non-MHC patients. The risk change after CRRC was similar for those with and without MHCs (0.10+/-0.13 vs 0.10+/-0.14; P=.82), but patients with MHCs had a longer CRRC enrollment (245+/-152 vs 205+/ 161 days; P<.03). The efficacy of the CRRC model to reduce cardiovascular risk is not attenuated by a concomitant MHC. PMID- 19476572 TI - Now or never: optimal antihypertensive therapy in the elderly. AB - Hypertension control rates in the elderly, particularly for systolic hypertension, are poor and lower than control rates in other age groups. Older patients often require treatment with specific antihypertensive drugs because of concomitant conditions and usually need > or =2 drugs to control blood pressure. Combining drugs with complementary mechanisms of action may improve both blood pressure control and the tolerability of individual drugs. A number of fixed-dose combinations have shown efficacy in older patients and in stage 2 hypertension, including various combinations involving diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. PMID- 19476573 TI - A longer course of varenicline therapy improves smoking cessation rates. AB - Smoking exerts strong dose-dependent increases in cardiovascular risk and mortality, and quitting can profoundly decrease these risks. Varenicline attenuates nicotine addiction by reducing withdrawal symptoms and cravings. A meta-analysis performed addressed whether a longer duration of varenicline is associated with better abstinence rates than shorter courses of treatment. For this meta-analysis, a literature search was performed to identify randomized controlled trials investigating the efficacy of the smoking cessation agent varenicline. The association between abstinence and duration of treatment was analyzed using fixed-effect meta-regression. Five randomized controlled trials were identified and included in this meta-analysis. A highly significant relationship (P<.001) was found between the length of exposure to varenicline and abstinence rate. Cessation rates were approximately twice as high with varenicline treatment of 24 weeks compared to 6 weeks. In conclusion, a meta analysis of randomized controlled trials suggests that longer duration of varenicline therapy improves long-term abstinence rates. PMID- 19476574 TI - Use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy to reduce cardiovascular events in high-risk patients: part 2. AB - As presented previously in Part 1 of this 2-part article, many long-term clinical trials provide overwhelming evidence of the benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) across the cardiovascular continuum. Trials also indicate additive or synergistic effects of combination therapy in renal disease and heart failure. Part 2, which is presented here, discusses the extensive interaction of the renin-angiotensin system (RAS) with the cellular and molecular pathophysiology of cardiovascular disease and the cross-continuum effects of ARBs and ACE inhibitors, which raises the possibility that RAS inhibition can offer protection in high-risk patients who do not have symptoms. Although trial evidence supports the effectiveness of monotherapy, the benefits of combined ACE inhibitor/ARB therapy in high-risk patients await confirmation. Ongoing clinical research will provide new and important information regarding the efficacy of specific combination (ACE inhibitor/ARB) therapies. PMID- 19476575 TI - The metabolic syndrome and cardiovascular disease: part 2. AB - In part 1 of this overview, the authors reviewed the epidemiology, definitions, pathophysiology, and interaction of inflammatory markers that are elaborated from the very active paracrine adipocyte. In part 2, they focus on the management of the metabolic syndrome. Management of this syndrome includes identification of individuals in the early stages of the syndrome and emphasizes the risk of developing diabetes mellitus and the progression to cardiovascular disease. This can be accomplished by simple physical examination and an assessment of routine laboratory findings, which should include measurement of fasting glucose, a lipid profile, and body morphometrics. A 10-year risk assessment is needed in patients who have a diagnosis of the metabolic syndrome. The most important therapeutic intervention in the metabolic syndrome is lifestyle change, with a focus on weight reduction and regular leisure time physical activity. PMID- 19476576 TI - Diabetes Control and Cardiovascular Risk: ACCORD, ADVANCE, AVOID, and SANDS. PMID- 19476577 TI - Winning at the weight loss game. PMID- 19476578 TI - The problem of stent thrombosis associated with drug-eluting stents and the optimal duration of dual antiplatelet therapy. AB - Drug-eluting stents have significantly reduced the problem of restenosis, but there is an association between drug-eluting stents and stent thrombosis that can be a significant clinical problem resulting in myocardial infarction or death. The risk for stent thrombosis increases in certain clinical situations and has been reduced through the use of dual antiplatelet therapy for prolonged periods. Until new therapies are developed, it is essential that patients who have had drug-eluting stents implanted continue with dual-antiplatelet therapy for at least 1 year and possibly for an indefinite period. PMID- 19476579 TI - Coronary heart disease and dyslipidemia: a cross-sectional evaluation of prevalence, current treatment, and clinical control in a large cohort of Spanish high-risk patients: the PRINCEPS study. AB - The authors assessed a large cohort of patients with coronary heart disease (CHD) or at high risk for developing CHD in terms of lipid profile, lipid-lowering treatment, and attainment of National Cholesterol Education Program (NCEP) target low-density lipoprotein cholesterol (LDL-C) levels. The investigation was a cross sectional study involving Spanish outpatients treated in primary or secondary care facilities. From a total of 26,598 attending patients, 12,128 with CHD or CHD risk equivalents were recruited by 1875 physicians; 49% had CHD and 69% had multiple risk factors. Only 25% of patients attained LDL-C values <100 mg/dL, 76.6% patients received lipid-lowering therapy (statins in 95.4% of cases), and 54% of physicians considered that a treatment change was required (the most frequent choice was the addition of ezetimibe to current statin therapy). In this large cohort of high-risk coronary patients, only 25% attained a target LDL-C of <100 mg/dL. These results highlight a need for improved patient care and physician awareness/training. PMID- 19476581 TI - Low-density lipoprotein reduction and magnitude of cardiovascular risk reduction. AB - The authors examined the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction and the magnitude of cardiovascular risk reduction. From the Veterans Integrated Service Network 1 databases, the authors selected 54,611 patients with prevalent ischemic heart disease, peripheral vascular disease or diabetes mellitus, and >or=2 documented LDL-C levels who were followed between 1997 and 2006. The outcome was defined as acute myocardial infarction or revascularization. Preoutcome LDL-C reduction was categorized as follows: <10 mg/dL, reference; >or=10 but <40 mg/dL, small reduction; >or=40 but <70 mg/dL, moderate reduction; >or=70 mg/dL, large reduction. Proportional hazards were used to determine the hazard ratio for the outcome for each LDL-C reduction category compared with the reference. Results revealed a graded relationship between the magnitude of reduction in LDL-C and cardiovascular risk reduction. Stratified analyses demonstrated these findings to be robust regardless of initial LDL-C levels or whether patients achieved "target" final LDL-C values of <100 mg/dL. PMID- 19476580 TI - Factors associated with low levels of subclinical vascular disease in older adults: multi-ethnic study of atherosclerosis. AB - Coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and reduced ankle brachial indices (ABI) are markers of subclinical vascular disease strongly associated with aging. The authors identified factors associated with low levels of subclinical vascular disease in 1824 participants 70 years and older in the Multi-Ethnic Study of Atherosclerosis. A total of 452 had low CAC (<25th percentile), 441 had low CIMT (<25th percentile), 1636 had normal ABI (>0.9), and 165 had a combination index indicating favorable values for all 3 parameters. This combination index was independently associated with younger age (odds ratio [OR] 2.5 per 1 SD [95% confidence interval (CI), 1.8-3.6]), female sex (OR 3.0 [95% CI, 1.9-4.8]), lower body mass index (OR 1.6 per 1 SD [95% CI, 1.2-2.0]), absence of hypertension (OR 1.8 [95% CI, 1.2-2.6]), absence of dyslipidemia (OR 1.6 [95% CI, 1.04-2.4]), and never-smoking (OR 1.7 [95% CI, 1.1-2.6]). No significant associations were observed for C-reactive protein, education, diet, or physical activity. Favorable levels of multiple traditional risk factors, but not several novel risk factors, were associated with subclinical markers of successful cardiovascular aging. PMID- 19476582 TI - Use of an electronic medical record to characterize cases of intermediate statin induced muscle toxicity. AB - Statin use can be accompanied by a variety of musculoskeletal complaints. The authors describe the clinical characteristics of case patients who experienced adverse statin-induced musculoskeletal symptoms within a large population-based cohort in Central Wisconsin. Case status was determined based on elevated serum creatine kinase (CK) levels and the presence of at least 1 physician note reflecting an increased index of suspicion for statin intolerance. From the medical records of nearly 2 million unique patients, the authors identified more than 20,000 potential study patients ( approximately 1%) having CK data and at least 1 exposure to a statin drug. Manual screening was completed on 2227 patients with CK levels in the upper 10th percentile. Of those screened, 267 met inclusion criteria (12.0% eligibility) and 218 agreed to participate in a retrospective study characterizing the risk determinants of statin-induced muscle toxicity. Three categoric pain variables were graded retrospectively (distribution, location, and severity of pain). The presenting complaints of the case patients were extremely heterogeneous. The number of patients with a compelling pain syndrome (diffuse, proximal muscle pain of high intensity) increased at higher serum CK levels; the number of patients with indeterminate pain variables decreased at higher serum CK levels. The lines reflecting these relationships cross at a CK level of approximately 1175 U/L, approximately half the threshold level needed to make a clinical diagnosis of "myopathy" (ie, CK >10 fold the upper limit of normal). PMID- 19476584 TI - Using impedance cardiography to detect subclinical cardiovascular disease in women with multiple risk factors: a pilot study. AB - Early detection of cardiovascular disease (CVD) could initiate appropriate treatment and prevent progression. This study used impedance cardiography (ICG) waveform analysis with postural change to detect functional CVD in women older than 40 years with no history of CVD and >or=2 of the following risk factors: cigarette smoking, poor diet, physical inactivity, central adiposity, family history of premature CVD, hypertension, and dyslipidemia. A study group of 32 women underwent ICG in standing and supine positions. An age-matched control group had 20 women with an active lifestyle, no risk factors, and no history of CVD. All women in the control group had normal ICG data. All women in the study group had some abnormal ICG data, with 28 (87.5%) having multiple ICG abnormalities. ICG data indicated that 13 (40.6%) had ventricular dysfunction, 14 (43.8%) had high vascular resistive load, and 30 (93.8%) had elevated vascular pulsatile load. The data suggest that subclinical CVD, detectable by ICG, is prevalent in women older than 40 years with multiple risk factors. Abnormal ICG results could expedite the initiation of customized treatment as part of a preventive approach to CVD. PMID- 19476583 TI - Appropriateness of cholesterol management in primary care by sex and level of cardiovascular risk. AB - A study was undertaken to ascertain the appropriateness of lipid screening and management per the Third Report of the Adult Treatment Panel National Cholesterol Education Program (ATP III) guideline in a sample of North Carolina primary care practices. Demographics, cholesterol values, and comorbid conditions were abstracted from the medical records from 60 community practices participating in a randomized practice-based trial (Guideline Adherence for Heart Health). Eligible patients were aged 21 to 84 years, seen during the baseline period of June 1, 2001, through May 31, 2003, and who were not taking lipid-lowering therapy. Multivariable logistic regression was utilized to assess whether age, sex, race/ethnicity, diabetes, cardiovascular disease, ATP III risk category, or pretreatment low-density lipoprotein (LDL) influenced treatment. Among 5031 eligible patients, 1711 (34.5%) received screening lipid profiles. Screening rates were higher with older age, diabetes, and cardiovascular disease. No large differences were seen by sex. Among patients screened (mean age, 51.6 years; 57.9% female), 76.6% were appropriately managed within 4 months. In adjusted analyses, older age was associated with less appropriate treatment (odds ratio [OR] per 5 years, 0.91; P=.01), and patients with LDL cholesterol or=190 mg/dL and those at high risk. Among 375 patients eligible for drug treatment, those with LDL levels between 131 and 159 mg/dL were much less likely to be treated (OR, 0.15; P<.001) compared with those with LDL >190 mg/dL, whereas risk category did not influence treatment. The challenge facing implementation of ATP III guidelines is much greater for intermediate- and high-risk patients than for low-risk patients. PMID- 19476585 TI - National Cholesterol Education Panel III guidelines performance role in preventing myocardial infarction in a large cohort without a history of coronary artery disease: Korea Acute Myocardial Infarction Registry study. AB - The Third Report of the Adult Treatment Panel National Cholesterol Education Program (NCEP-ATP III) guidelines are widely used for the primary prevention of a coronary event. These guidelines were developed using experimental data from studies that enrolled mostly Caucasian patients. The pathogenesis of atherosclerosis varies with ethnicity. Given these two circumstances, the authors sought to investigate the performance of the guidelines in a large Asian cohort. The Korea Acute Myocardial Infarction Registry (KAMIR) includes data collected between November 2005 and December 2006 from 41 referral centers in South Korea. A retrospective review of the clinical data was performed. After patients with a history of coronary heart disease (CHD), CHD equivalent, and those taking lipid lowering medications were excluded, 2969 individuals (76% men; 61+/-12 years) were enrolled. The recommendations for lipid-lowering treatments according to the NCEP-ATP III were examined in the context of the cohort. A total of 38%, 66%, and 8% of the study participants had hypertension, were smokers, and had a family history of premature CHD, respectively. When patients were stratified by the number of risk factors present and their 10-year CHD risk, 69% diagnosed with an acute myocardial infarction did not qualify for drug therapy. Irrespective of the age group examined (young, intermediate, and old), the percentage of patients who did not qualify for a lipid-lowering pharmacologic intervention was higher than 60%. NCEP-ATP III underestimates CHD risk in individuals of Asian descent. Further studies are needed to improve primary CHD prevention in this patient population. PMID- 19476586 TI - Jupiter and accomplish. PMID- 19476587 TI - Colored-speech synaesthesia is triggered by multisensory, not unisensory, perception. AB - Although it is estimated that as many as 4% of people experience some form of enhanced cross talk between (or within) the senses, known as synaesthesia, very little is understood about the level of information processing required to induce a synaesthetic experience. In work presented here, we used a well-known multisensory illusion called the McGurk effect to show that synaesthesia is driven by late, perceptual processing, rather than early, unisensory processing. Specifically, we tested 9 linguistic-color synaesthetes and found that the colors induced by spoken words are related to what is perceived (i.e., the illusory combination of audio and visual inputs) and not to the auditory component alone. Our findings indicate that color-speech synaesthesia is triggered only when a significant amount of information processing has occurred and that early sensory activation is not directly linked to the synaesthetic experience. PMID- 19476588 TI - Body locomotion as regulatory process: stepping backward enhances cognitive control. PMID- 19476589 TI - Compensatory conscientiousness and health in older couples. AB - The present study tested the effect of conscientiousness and neuroticism on health and physical limitations in a representative sample of older couples (N= 2,203) drawn from the Health and Retirement Study. As in past research, conscientiousness predicted better health and physical functioning, whereas neuroticism predicted worse health and physical functioning. Unique to this study was the finding that conscientiousness demonstrated a compensatory effect, such that husbands' conscientiousness predicted wives' health outcomes above and beyond wives' own personality. The same pattern held true for wives' conscientiousness as a predictor of husbands' health outcomes. Furthermore, conscientiousness and neuroticism acted synergistically, such that people who scored high for both traits were healthier than others. Finally, we found that the combination of high conscientiousness and high neuroticism was also compensatory, such that the wives of men with this combination of personality traits reported better health than other women. PMID- 19476590 TI - Pathological video-game use among youth ages 8 to 18: a national study. AB - Researchers have studied whether some youth are "addicted" to video games, but previous studies have been based on regional convenience samples. Using a national sample, this study gathered information about video-gaming habits and parental involvement in gaming, to determine the percentage of youth who meet clinical-style criteria for pathological gaming. A Harris poll surveyed a randomly selected sample of 1,178 American youth ages 8 to 18. About 8% of video game players in this sample exhibited pathological patterns of play. Several indicators documented convergent and divergent validity of the results: Pathological gamers spent twice as much time playing as nonpathological gamers and received poorer grades in school; pathological gaming also showed comorbidity with attention problems. Pathological status significantly predicted poorer school performance even after controlling for sex, age, and weekly amount of video-game play. These results confirm that pathological gaming can be measured reliably, that the construct demonstrates validity, and that it is not simply isomorphic with a high amount of play. PMID- 19476592 TI - Forgetting the unforgettable through conversation: socially shared retrieval induced forgetting of September 11 memories. AB - A speaker's selective recounting of memories shared with a listener will induce both the speaker and the listener to forget unmentioned, related material more than unmentioned, unrelated material. We extended this finding of within individual and socially shared retrieval-induced forgetting to well-rehearsed, emotionally intense memories that are similar for the speaker and listener, but differ in specifics. A questionnaire probed participants' memory of the September 11 terrorist attacks. Questions and responses were grouped into category-exemplar structures. Then, participants selectively rehearsed their answers (using a structured interview in Experiment 1 and a joint recounting between pairs in Experiment 2). In subsequent recognition tests, response times yielded evidence of within-individual retrieval-induced forgetting and socially shared retrieval induced forgetting. This result indicates that conversations can alter memories of speakers and listeners in similar ways, even when the memories differ. We discuss socially shared retrieval-induced forgetting as a mechanism for the formation of collective memories. PMID- 19476591 TI - "Really? She blicked the baby?": two-year-olds learn combinatorial facts about verbs by listening. AB - Children use syntax to guide verb learning. We asked whether the syntactic structure in which a novel verb occurs is meaningful to children even without a concurrent scene from which to infer the verb's semantic content. In two experiments, 2-year-olds observed dialogues in which interlocutors used a new verb in transitive ("Jane blicked the baby!") or intransitive ("Jane blicked!") sentences. The children later heard the verb in isolation ("Find blicking!") while watching a one-participant event and a two-participant event presented side by side. Children who had heard transitive dialogues looked reliably longer at the two-participant event than did those who had heard intransitive dialogues. This effect persisted even when children were tested on a different day, but disappeared when no novel verb accompanied the test events (Experiment 2). Thus, 2-year-olds gather useful combinatorial information about a novel verb simply from hearing it in sentences, and later retrieve that information to guide interpretation of the verb. PMID- 19476593 TI - Bad drives psychological reactions, but good propels behavior: responses to honesty and deception. AB - Research across disciplines suggests that bad is stronger than good and that individuals punish deception more than they reward honesty. However, methodological issues in previous research limit the latter conclusion. Three experiments resolved these issues and consistently found the opposite pattern: Individuals rewarded honesty more frequently and intensely than they punished deception. Experiment 2 extended these counterintuitive findings by revealing a divergence between evaluation and behavior: Evaluative reactions to deception were stronger than those to honesty, but behavioral intentions in response to honesty were stronger than those in response to deception. In addition, individuals wanted to avoid deceivers more than they wanted to approach honest actors. Experiment 3 found that punishment, but not reward, frequencies were sensitive to costs. Moderated-mediation tests revealed the role of different psychological mechanisms: Negative affect drove punishments, whereas perceived trustworthiness drove rewards. Overall, bad appears to be stronger than good in influencing psychological reactions, but good seems to be stronger than bad in influencing behavior. PMID- 19476594 TI - The enhancement of visuospatial processing efficiency through Buddhist Deity meditation. AB - This study examined the effects of meditation on mental imagery, evaluating Buddhist monks' reports concerning their extraordinary imagery skills. Practitioners of Buddhist meditation were divided into two groups according to their preferred meditation style: Deity Yoga (focused attention on an internal visual image) or Open Presence (evenly distributed attention, not directed to any particular object). Both groups of meditators completed computerized mental imagery tasks before and after meditation. Their performance was compared with that of control groups, who either rested or performed other visuospatial tasks between testing sessions. The results indicate that all the groups performed at the same baseline level, but after meditation, Deity Yoga practitioners demonstrated a dramatic increase in performance on imagery tasks compared with the other groups. The results suggest that Deity meditation specifically trains one's capacity to access heightened visuospatial processing resources, rather than generally improving visuospatial imagery abilities. PMID- 19476595 TI - Prelinguistic infants, but not chimpanzees, communicate about absent entities. AB - One of the defining features of human language is displacement, the ability to make reference to absent entities. Here we show that prelinguistic, 12-month-old infants already can use a nonverbal pointing gesture to make reference to absent entities. We also show that chimpanzees-who can point for things they want humans to give them-do not point to refer to absent entities in the same way. These results demonstrate that the ability to communicate about absent but mutually known entities depends not on language, but rather on deeper social-cognitive skills that make acts of linguistic reference possible in the first place. These nonlinguistic skills for displaced reference emerged apparently only after humans' divergence from great apes some 6 million years ago. PMID- 19476596 TI - The cryoprotective effect of trehalose supplementation on boar spermatozoa quality. AB - In order to improve boar sperm quality during frozen-thawed process, the influence of the presence of trehalose on success of cryopreservation of boar sperm were investigated. We evaluated freeze-thawing tolerance of boar spermatozoa in a base cooling extender with the addition of different trehalose concentrations (0, 25, 50, 100 and 200 mm), and try to determine the optimum concentration of trehalose. We chose sperm motility, mitochondrial activity, acrosome integrity and membrane integrity as parameters to evaluate cryopreservation capacity of boar spermatozoa. We obtained the best results for 100 mm trehalose-supplemented extenders, with values of 49.89% for motility, 44.69% for mitochondrial activity, 66.52% for acrosome integrity and 44.61% for membrane integrity, while freeze-thawing tolerance diminished significantly for 200 . The synergic effect of trehalose and glycerol resulted in better cryosurvival of boar spermatozoa than that of a single cryoprotectant. In conclusion, when trehalose-supplementation was added up to 100 mm, trehalose confers a greater cryoprotective capacity to the extender, and the sperm motility, mitochondrial activity, membrane integrity and acrosome integrity parameters were significantly improved during frozen-thawed process. PMID- 19476597 TI - Preoperative use of inhaled tiotropium in lung cancer patients with untreated COPD. AB - BACKGROUND AND OBJECTIVE: Lung cancer patients with COPD are at high risk during surgery. Tiotropium, a long-acting bronchodilator, is a preferred maintenance therapy for COPD, but its efficacy in the perioperative period has not been clarified. METHODS: A retrospective review was performed of the medical records of 102 patients with primary lung cancer and COPD, who underwent scheduled surgery. Twenty-one lung cancer patients with untreated mild-to-severe COPD received tiotropium preoperatively. Spirometry was performed prior to and after 2 weeks of treatment with tiotropium, and at 3 months after surgery. RESULTS: Two week preoperative treatment with tiotropium significantly improved respiratory symptoms and pulmonary function as reflected by FVC (median 3.43 L pretreatment vs 3.52 L post-treatment), FEV(1) (median 2.06 L vs 2.32 L) and FEV(1)% (73.2% vs 81.0%) (all P < 0.001). Postoperative FEV(1)% was significantly increased from a median of 56.0% (interquartile range 51.6-60.3) to 63.4% (60.8-66.0) (P < 0.001). The increase in FEV(1) was inversely associated with severity of COPD (r = -0.59, P < 0.005). Lung resections were successfully accomplished without complications. The postoperative FEV(1) predicted prior to tiotropium treatment was underestimated (median predicted postoperative FEV(1) 1.65 L vs median measured postoperative FEV(1) 1.96 L, P < 0.001). CONCLUSIONS: Preoperative treatment with tiotropium may facilitate surgical treatment for lung cancer patients with COPD. This is encouraging for COPD patients who may require curative lung resections. PMID- 19476599 TI - The effect of obesity and smoking status on lung age in Japanese men. AB - BACKGROUND AND OBJECTIVE: The lung age of smokers is greater than their real age. We have had the clinical impression that the lung age of non-smokers might be older than their real age and that obese subjects with decreased VC and FEV1 would also have an increased lung age. This cross-sectional study investigated the relationships between lung age and smoking status, and lung age and BMI. METHODS: Subjects comprised 3247 men who consulted our institute for health screening; 819 subjects were non-smokers. In smokers and non-smokers, lung age estimated by the predictive equation based on height and FEV1 was compared with chronological age. To investigate the relationship between lung age and BMI in non-smokers, subjects were categorized into four groups based on quartiles of BMI and the lung age of the four groups compared. Multiple linear regression was used to determine the relative contribution of BMI and smoking status to lung age. RESULTS: The predictive equation used to estimate lung age significantly overestimated the chronological age of study subjects. In non-smokers, higher BMI was significantly associated with higher lung age. BMI, duration of smoking and number of cigarettes per day were significantly associated with increased lung age. CONCLUSIONS: Lung age could be used to motivate lifestyle change in obese individuals. PMID- 19476598 TI - Transpleural perfusion with oxygenated perfluorocarbon increases systemic oxygenation. AB - BACKGROUND AND OBJECTIVE: There is a need for new methods of increasing systemic oxygenation in patients with hypoxia due to potentially reversible pulmonary failure. The goal of this study was to determine if it is possible to increase systemic oxygenation by perfusing the thoracic cavity with oxygenated perfluorocarbon in animals with induced hypoxia. METHODS: Fifteen Sprague-Dawley rats were intubated, and hypoxia was induced by hypoventilation (room air, respiratory rate <30/min). Inflow and outflow tubes were placed in the thoracic cavity and connected to a perfusion circuit containing a roller pump, warmer and oxygenator. Rats in Group I were not treated during hypoventilation, those in Group II were perfused with oxygenated saline, and those in Group III were perfused with oxygenated perfluorocarbon. Arterial blood gases were collected every 30 min for 180 min. At the conclusion of the experiments, pathological examination of the lungs and parietal pleura was performed. RESULTS: PaO2 in Group III was significantly higher than that in Group I or Group II. PaCO2 in Group III was significantly lower than that in the other two groups. Histological examination showed no damage to the lungs and parietal pleura in Group III. CONCLUSIONS: Perfusion of the thoracic cavity with oxygenated perfluorocarbon in an animal model of induced hypoxia resulted in a significant increase in systemic oxygenation without lung damage and might be a useful method for improving systemic oxygenation. PMID- 19476600 TI - Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnoea syndrome. AB - BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is known to be a risk factor for cardiovascular events. However, the precise mechanism has not been fully elucidated. OSAS-induced hypoxic stress may promote the production of inflammatory cytokines and chemokines by monocytes, which has a crucial role in the development of atherosclerosis. In addition, adhesion to the vascular endothelium and transendothelial migration of monocytes are considered to induce atherosclerosis. The aim of this study was to investigate the effects of hypoxic stress on the invasive ability of monocytes in OSAS. METHODS: Twenty-one male patients with OSAS and 17 healthy male control subjects, who were matched for age and BMI, were enrolled. Venous blood samples were collected before and after sleep, and also after CPAP titration, for the purpose of monocyte isolation. The invasive ability of monocytes was evaluated by counting the number of invading cells using a BD BioCoat Matrigel Invasion Chamber. RESULTS: The number of cells, which represents the invasive ability of monocytes, was significantly higher in patients with OSAS compared with control subjects, in the early morning (P < 0.001). In patients with OSAS, invasive ability in the early morning after sleep was significantly elevated as compared with that before sleep (P < 0.001), and was positively correlated with the oxygen desaturation index (P < 0.05). CPAP titration led to a decrease in the invasive ability (P < 0.001). CONCLUSIONS: These results indicate that OSAS-induced hypoxic stress activates the invasive ability of monocytes, and that the occurrence of this phenomenon during sleep may contribute to the development of atherosclerosis in OSAS. PMID- 19476601 TI - Pulmonary alveolar proteinosis in China: a systematic review of 241 cases. AB - BACKGROUND AND OBJECTIVE: Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease. It was first described in China in 1965, and more cases have been reported subsequently. A systematic review was performed on 241 cases of PAP in China and progress in the diagnosis and treatment of this disease is discussed. METHODS: The Chinese biological and medical databases from 1965 to 2006 were searched and 241 cases with complete clinical and pathological data were identified. The clinical characteristics of the disease were summarized and longitudinal comparisons were made of diagnostic and treatment methods over time. RESULTS: The morbidity associated with PAP has increased in recent years. The clinical manifestations were non-specific. Progressive dyspnoea, cough and sputum were the most common symptoms. The percentage of patients undergoing CT examination has increased over the years. The combination of bronchoscopic biopsy and bronchoalveolar lavage (BAL) was usually sufficient to establish the diagnosis. Treatment was reported for a total of 142 cases. BAL and whole lung lavage were both effective and were only required once by most patients. CONCLUSIONS: The demographic characteristics and clinical manifestations of PAP patients in China are largely consistent with previous reports. Morbidity has increased dramatically in recent years, mainly due to the broad application of bronchoscopy since 1995. CT is very important for diagnosis of the disease. The long-term effects of treatment by whole lung lavage and BAL are similar. PMID- 19476602 TI - Association of impaired respiratory function with urinary incontinence. AB - BACKGROUND AND OBJECTIVE: This study investigated the relationship between urinary incontinence and respiratory function in middle-aged and older Japanese men. METHODS: Seven hundred community-dwelling men aged 40 years or above were recruited from community centres and hospital outpatient clinics. The International Consultation on Incontinence Questionnaire-Short Form was administered to ascertain their urinary incontinence status. Standardized spirometric measurements of respiratory function were performed. RESULTS: The prevalence of urinary incontinence was 7.6% among the 668 eligible participants (mean age 62.7 years). The 51 men who leaked urine had significantly lower FEV1 and FVC than those who were continent (P < 0.01). The adjusted risks of urinary incontinence were 0.67 (95% CI: 0.43-1.04) and 0.63 (95% CI: 0.40-0.98) for the two continuous respiratory function variables (L), respectively. CONCLUSION: The findings indicate an inverse association between urinary incontinence and respiratory function and an additional health burden in lung diseases. PMID- 19476603 TI - Electrical impedance tomography is able to track changes in respiratory function in endotoxin-challenged rodents. AB - BACKGROUND AND OBJECTIVE: In order to assess and optimize the effect of new therapies for acute lung injury (ALI) in rodent models, a monitoring technique that continuously assesses the functional state of the lung is mandatory. Electrical impedance tomography (EIT) has been suggested as a technique for quantifying lung inflammation in ALI. However, EIT has not been evaluated in a rodent model of ALI. METHODS: EIT measurements were compared in ventilated Sprague-Dawley rats (n = 14), randomly subjected to intratracheal administration of endotoxin (LPS) or saline (control). Lung mechanics, lung weight wet/dry ratio and inflammatory markers in bronchoalveolar lavage fluid were also evaluated. RESULTS: LPS caused a significant decrease in lung compliance and TLC as compared with control (-42.0%, P = 0.04, and -27.9%, P = 0.02, respectively). These changes were paralleled by differences in mean impedance changes as detected by EIT (Spearman's rank correlation coefficient: rho = 0.66 and 0.73, respectively, P < 0.01). LPS increased the lung weight wet/dry ratio (6.35 +/- 0.42 vs 5.15 +/- 0.07, P = 0.003), and the bronchoalveolar lavage total WCC (8.96 +/- 1.87 vs 1.16 +/- 0.10 x 10(9)/L, P = 0.002) as compared with control. The lung weight wet/dry ratio was inversely related to the mean impedance change (rho = -0.76, P < 0.01). CONCLUSIONS: This study has demonstrated for the first time that eight-electrode EIT readily tracks the inflammatory response of lung tissue in a rodent model of ALI. EIT may thus provide a promising, non-invasive technique for monitoring the time-course of ALI in rodent models, and for testing novel pharmacological strategies to counter it. PMID- 19476604 TI - Osteopontin is upregulated in malignant and inflammatory pleural effusions. AB - BACKGROUND AND OBJECTIVE: Osteopontin (OPN) is an important mediator of inflammation and cancer progression. In the present study, we asked whether pleural fluid (PF) and serum OPN concentrations differed between patients with pleural effusions of different aetiologies, and whether assessment of OPN levels was useful for diagnostic purposes. METHODS: One hundred and nine consecutive patients with pleural effusions of different aetiologies were recruited prospectively during daily clinics. OPN levels were measured by ELISA. RESULTS: PF OPN levels were 10-fold higher in exudates than in transudates and were significantly correlated with markers of pleural inflammation and vascular hyper permeability, such as PF/serum LDH or protein ratios, PF protein and PF vascular endothelial growth factor levels. Patients with malignant pleural effusions had higher PF and lower serum OPN concentrations than those with benign disease. The diagnostic accuracies of PF and PF/serum OPN for malignancy were 71.5% (95% CI: 64-80) and 70.6% (95% CI: 62-80), respectively. CONCLUSIONS: OPN levels were elevated in exudative pleural effusions, as compared with the levels in blood or transudative pleural effusions. While PF and PF/serum OPN were higher in patients with malignancies, the diagnostic accuracy of the tests was not sufficient to permit routine use in clinical practice. PMID- 19476605 TI - Consecutive national surveys of ABO-incompatible blood transfusion in Japan. AB - BACKGROUND AND OBJECTIVES: Morbidity and mortality from ABO-incompatible transfusion persist as consequences of human error. Even so, insufficient attention has been given to improving transfusion safety within the hospital. MATERIALS AND METHODS: National surveys of ABO-incompatible blood transfusions were conducted by the Japanese Society of Blood Transfusion, with support from the Ministry of Health, Labor and Welfare. Surveys concluded in 2000 and 2005 analysed ABO-incompatible transfusion data from the previous 5 years (January 1995 to December 1999 and January 2000 to December 2004, respectively). The first survey targeted 777 hospitals and the second, 1355 hospitals. Data were collected through anonymous questionnaires. RESULTS: The first survey achieved a 77.4% response rate (578 of 777 hospitals). The second survey collected data from 251 more hospitals, but with a lower response rate (61.2%, or 829 of 1355 hospitals). The first survey analysed 166 incidents from 578 hospitals, vs. 60 incidents from 829 hospitals in the second survey. The main cause of ABO-incompatible transfusion was identification error between patient and blood product: 55% (91 of 166) in the first survey and 45% (27 of 60) in the second. Patient outcomes included nine preventable deaths from 1995 to 1999, and eight preventable deaths from 2000 to 2004. CONCLUSION: Misidentification at the bedside persists as the main cause of ABO-incompatible transfusion. PMID- 19476607 TI - The light of evolution. PMID- 19476608 TI - Risk of cancer in the vicinity of municipal solid waste incinerators: importance of using a flexible modelling strategy. AB - BACKGROUND: We conducted an ecological study in four French administrative departments and highlighted an excess risk in cancer morbidity for residents around municipal solid waste incinerators. The aim of this paper is to show how important are advanced tools and statistical techniques to better assess weak associations between the risk of cancer and past environmental exposures. METHODS: The steps to evaluate the association between the risk of cancer and the exposure to incinerators, from the assessment of exposure to the definition of the confounding variables and the statistical analysis carried out are detailed and discussed. Dispersion modelling was used to assess exposure to sixteen incinerators. A geographical information system was developed to define an index of exposure at the IRIS level that is the geographical unit we considered. Population density, rural/urban status, socio-economic deprivation, exposure to air pollution from traffic and from other industries were considered as potential confounding factors and defined at the IRIS level. Generalized additive models and Bayesian hierarchical models were used to estimate the association between the risk of cancer and the index of exposure to incinerators accounting for the confounding factors. RESULTS: Modelling to assess the exposure to municipal solid waste incinerators allowed accounting for factors known to influence the exposure (meteorological data, point source characteristics, topography). The statistical models defined allowed modelling extra-Poisson variability and also non-linear relationships between the risk of cancer and the exposure to incinerators and the confounders. CONCLUSION: In most epidemiological studies distance is still used as a proxy for exposure. This can lead to significant exposure misclassification. Additionally, in geographical correlation studies the non-linear relationships are usually not accounted for in the statistical analysis. In studies of weak associations it is important to use advanced methods to better assess dose response relationships with disease risk. PMID- 19476609 TI - Toxoplasma seroprevalence in a rural population in France: detection of a household effect. AB - BACKGROUND: Toxoplasma gondii, the agent of toxoplasmosis, has a complex life cycle. In humans, the parasite may be acquired either through ingestion of contaminated meat or through oocysts present in the environment. The importance of each source of contamination varies locally according to the environment characteristics and to differences concerning human eating habits and the presence of cats; thus, the risk factors may be determined through fine-scale studies. Here, we searched for factors associated with seropositivity in the population of two adjacent villages in Lorraine region, France. METHODS: All voluntary inhabitants filled out a questionnaire and gave a blood sample. The seroprevalence was estimated globally and according to the inhabitants' ages using a cubic spline regression. A mixed logistic regression model was used to quantify the effect of individual and household factors on the probability of seropositivity. RESULTS: Based on serological results from 273 persons, we estimated seroprevalence to be 47% (95% confidence interval: 41 to 53%). That seroprevalence increased with age: the slope was the steepest up to the age of 40 years (OR = 2.48 per 10-year increment, 95% credibility interval: [1.29 to 5.09]), but that increase was not significant afterwards. The probability of seropositivity tended to be higher in men than in women (OR = 2.01, 95% credibility interval: [0.92 to 4.72]) and in subjects eating raw vegetables at least once a week than in the others (OR = 8.4, 95% credibility interval: [0.93 to 72.1]). These effects were close to statistical significance. The multivariable analysis highlighted a significant seroprevalence heterogeneity among households. That seroprevalence varied between 6 and 91% (5th and 95th percentile of the household seropositivity distribution). CONCLUSION: The major finding is the household effect, with a strong heterogeneity of seroprevalence among households. This effect may be explained by common exposures of household members to local risk factors. Future work will quantify the link between the presence of oocysts in the soil and the seroprevalence of exposed households using a spatial analysis. PMID- 19476610 TI - Perceived neighborhood safety and incident mobility disability among elders: the hazards of poverty. AB - BACKGROUND: We investigated whether lack of perceived neighborhood safety due to crime, or living in high crime neighborhoods was associated with incident mobility disability in elderly populations. We hypothesized that low-income elders and elders at retirement age (65 - 74) would be at greatest risk of mobility disability onset in the face of perceived or measured crime-related safety hazards. METHODS: We conducted the study in the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE), a longitudinal cohort study of community-dwelling elders aged 65 and older who were residents of New Haven, Connecticut in 1982. Elders were interviewed beginning in 1982 to assess mobility (ability to climb stairs and walk a half mile), perceptions of their neighborhood safety due to crime, annual household income, lifestyle characteristics (smoking, alcohol use, physical activity), and the presence of chronic co-morbid conditions. Additionally, we collected baseline data on neighborhood crime events from the New Haven Register newspaper in 1982 to measure local area crime rates at the census tract level. RESULTS: At baseline in 1982, 1,884 elders were without mobility disability. After 8 years of follow-up, perceiving safety hazards was associated with increased risk of mobility disability among elders at retirement age whose incomes were below the federal poverty line (HR 1.56, 95% CI 1.02 - 2.37). No effect of perceived safety hazards was found among elders at retirement age whose incomes were above the poverty line. No effect of living in neighborhoods with high crime rates (measured by newspaper reports) was found in any sub-group. CONCLUSION: Perceiving a safety hazard due to neighborhood crime was associated with increased risk of incident mobility disability among impoverished elders near retirement age. Consistent with prior literature, retirement age appears to be a vulnerable period with respect to the effect of neighborhood conditions on elder health. Community violence prevention activities should address perceived safety among vulnerable populations, such as low-income elders at retirement age, to reduce future risks of mobility disability. PMID- 19476611 TI - Varicella vaccination in Europe - taking the practical approach. AB - Varicella is a common viral disease affecting almost the entire birth cohort. Although usually self-limiting, some cases of varicella can be serious, with 2 to 6% of cases attending a general practice resulting in complications. The hospitalisation rate for varicella in Europe ranges from 1.3 to 4.5 per 100,000 population/year and up to 10.1% of hospitalised patients report permanent or possible permanent sequelae (for example, scarring or ataxia). However, in many countries the epidemiology of varicella remains largely unknown or incomplete. In countries where routine childhood vaccination against varicella has been implemented, it has had a positive effect on disease prevention and control. Furthermore, mathematical models indicate that this intervention strategy may provide economic benefits for the individual and society. Despite this evidence and recommendations for varicella vaccination by official bodies such as the World Health Organization, and scientific experts in the field, the majority of European countries (with the exception of Germany and Greece) have delayed decisions on implementation of routine childhood varicella vaccination, choosing instead to vaccinate high-risk groups or not to vaccinate at all. In this paper, members of the Working Against Varicella in Europe group consider the practicalities of introducing routine childhood varicella vaccination in Europe, discussing the benefits and challenges of different vaccination options (vaccination vs. no vaccination, routine vaccination of infants vs. vaccination of susceptible adolescents or adults, two doses vs. one dose of varicella vaccine, monovalent varicella vaccines vs. tetravalent measles, mumps, rubella and varicella vaccines, as well as the optimal interval between two doses of measles, mumps, rubella and varicella vaccines). Assessment of the epidemiology of varicella in Europe and evidence for the effectiveness of varicella vaccination provides support for routine childhood programmes in Europe. Although European countries are faced with challenges or uncertainties that may have delayed implementation of a childhood vaccination programme, many of these concerns remain hypothetical and with new opportunities offered by combined measles, mumps, rubella and varicella vaccines, reassessment may be timely. PMID- 19476612 TI - Involvement of RNA-binding protein Hfq in the osmotic-response regulation of invE gene expression in Shigella sonnei. AB - BACKGROUND: The expression of Type III secretion system (TTSS) in Shigella is regulated in response to changes in environmental osmolarity and temperature. Temperature-dependent regulation of virF, the master regulator of TTSS synthesis, is believed to occur at the transcriptional level. We recently demonstrated, however, that TTSS synthesis also involves post-transcriptional regulation of the synthesis of InvE, a target of virF and key regulator of TTSS synthesis. The mRNA levels of invE (virB) are stable at 37 degrees C, but mRNA stability markedly decreases at low temperatures where the TTSS synthesis is tightly repressed. Deletion of hfq, which encodes an RNA chaperone in Gram-negative bacteria, results in the restoration of expression of invE and other TTSS genes at low temperature due to an increase in the stability of invE mRNA. To date, the molecular details of the regulation of TTSS expression in response to osmotic pressure are not known. In the current study, we investigated the mechanism of regulation of TTSS by osmotic pressure. RESULTS: Transcription of virF, which encodes the master regulator of TTSS expression, was partially repressed under low osmotic conditions. Several lines of evidence indicated that osmolarity dependent changes in TTSS synthesis are controlled at the post-transcriptional level, through the regulation of InvE synthesis. First, the expression InvE protein was tightly repressed under low osmotic growth conditions, even though invE mRNA transcripts were readily detectable. Second, under low osmotic conditions, invE mRNA was rapidly degraded, whereas deletion of hfq, which encodes an RNA chaperone, resulted in increased invE mRNA stability and the production of InvE protein. Third, the binding of purified Hfq in vitro to invE RNA was stronger in low-salt buffer, as assessed by gel-shift analysis and surface plasmon resonance (Biacore analysis). CONCLUSION: Osmolarity-dependent changes in TTSS synthesis in Shigella involve the post-transcriptional regulation of InvE expression, in addition to partial transcriptional activation by virF. The stability of invE mRNA is reduced under low osmotic conditions, similar to the effect of temperature. Deletion of an RNA chaperone gene (hfq) abolished the repression of TTSS synthesis at low osmolarity through a mechanism that involved increased stability of invE mRNA. We propose that the expression of Shigella virulence genes in response to both osmolarity and temperature involves the post transcriptional regulation of expression of InvE, a critical regulator of TTSS synthesis. PMID- 19476615 TI - Bronchial stump reinforcement with an azygous vein flap. AB - Bronchial stump reinforcement has been shown to significantly reduce the incidence of bronchopleural fistulas. Various coverage techniques have been described in the literature. While the azygous vein flap is an easy, safe and effective reinforcement option for right-sided bronchial stumps, the flap is not widely adopted, with little mention in the literature, partly due to surgeons' uneasiness with the technique. In this report, we describe an easy-to-adopt approach to azygous vein bronchial reinforcement. PMID- 19476614 TI - Current evidence on the burden of head and neck cancers in Nigeria. AB - BACKGROUND: Head and neck cancers (HNC) constitute 5-8% of total body cancers in Europe and America. It is difficult to appreciate the problem of cancers in Nigeria because most studies available are hospital-based studies. The aim of this study is to highlight current evidence on the burden of head and neck cancers in Nigeria based on literature review and to discuss potential health care actions to improve management. METHODS: A literature search using Medline was conducted for publications on head and neck cancer in Nigeria. Identified publications were manually searched for additional relevant non-Medline articles or abstracts. The full-texts of these articles were thoroughly examined for the occurrence, distribution, identified risks factors, presentations, diagnostic method, treatment, prognosis and challenges associated with the management of HNC. RESULTS: A total of twenty-seven relevant published articles on Head and neck cancers from 1968 to 2008 were reviewed. The age of patients with HNC ranged from nine months to over 80 years with peak between 3-6th decade of life. The male to female ratio ranged from 1:1 to 2.3:1. Identified risks factors were scanty, namely kola nuts and tobacco chewing, tobacco smoking, farming, viral infections, alcohol and smoking. Reports on the overall pattern of Head and neck cancers from different regions of the country cited nasopharynx as the commonest site for HNC, the sino-nasal is the second commonest while larynx, is the third commonly affected site. The majority of HNC was epithelial in origin and was mostly squamous cell carcinoma. Late presentation with advanced disease is common and treatment in most cases is palliative either with surgery or chemotherapy, and radiotherapy when available. There are few reports on the outcome of HNC treatment in Nigeria. CONCLUSION: The burden of managing HNC in Nigeria is enormous and the government should set up the National Cancer Institute with a view of educating the public on cancer prevention, detection and treatment. PMID- 19476613 TI - DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo. AB - INTRODUCTION: B cells have many different roles in systemic lupus erythematosus (SLE), ranging from autoantigen recognition and processing to effector functions (for example, autoantibody and cytokine secretion). Recent studies have shown that intracellular nucleic acid-sensing receptors, Toll-like receptor (TLR) 7 and TLR9, play an important role in the pathogenesis of SLE. Dual engagement of rheumatoid factor-specific AM14 B cells through the B-cell receptor (BCR) and TLR7/9 results in marked proliferation of autoimmune B cells. Thus, strategies to preferentially block innate activation through TLRs in autoimmune B cells may be preferred over non-selective B-cell depletion. METHODS: We have developed a new generation of DNA-like compounds named class R inhibitory oligonucleotides (INH ODNs). We tested their effectiveness in autoimmune B cells and interferon-alpha producing dendritic cells in vitro and in lupus-prone MRL-Faslpr/lpr mice in vivo. RESULTS: Class R INH-ODNs have 10- to 30-fold higher inhibitory potency when autoreactive B cells are synergistically activated through the BCR and associated TLR7 or 9 than when stimulation occurs via non-BCR-engaged TLR7/9. Inhibition of TLR9 requires the presence of both CCT and GGG triplets in an INH ODN, whereas the inhibition of the TLR7 pathway appears to be sequence independent but dependent on the phosphorothioate backbone. This difference was also observed in the MRL-Faslpr/lpr mice in vivo, where the prototypic class R INH-ODN was more effective in curtailing abnormal autoantibody secretion and prolonging survival. CONCLUSIONS: The increased potency of class R INH-ODNs for autoreactive B cells and dendritic cells may be beneficial for lupus patients by providing pathway-specific inhibition yet allowing them to generate protective immune response when needed. PMID- 19476616 TI - A simulation analysis to characterize the dynamics of vaccinating behaviour on contact networks. AB - BACKGROUND: Human behavior influences infectious disease transmission, and numerous "prevalence-behavior" models have analyzed this interplay. These previous analyses assumed homogeneously mixing populations without spatial or social structure. However, spatial and social heterogeneity are known to significantly impact transmission dynamics and are particularly relevant for certain diseases. Previous work has demonstrated that social contact structure can change the individual incentive to vaccinate, thus enabling eradication of a disease under a voluntary vaccination policy when the corresponding homogeneous mixing model predicts that eradication is impossible due to free rider effects. Here, we extend this work and characterize the range of possible behavior prevalence dynamics on a network. METHODS: We simulate transmission of a vaccine preventable infection through a random, static contact network. Individuals choose whether or not to vaccinate on any given day according to perceived risks of vaccination and infection. RESULTS: We find three possible outcomes for behavior-prevalence dynamics on this type of network: small final number vaccinated and final epidemic size (due to rapid control through voluntary ring vaccination); large final number vaccinated and significant final epidemic size (due to imperfect voluntary ring vaccination), and little or no vaccination and large final epidemic size (corresponding to little or no voluntary ring vaccination). We also show that the social contact structure enables eradication under a broad range of assumptions, except when vaccine risk is sufficiently high, the disease risk is sufficiently low, or individuals vaccinate too late for the vaccine to be effective. CONCLUSION: For populations where infection can spread only through social contact network, relatively small differences in parameter values relating to perceived risk or vaccination behavior at the individual level can translate into large differences in population-level outcomes such as final size and final number vaccinated. The qualitative outcome of rational, self interested behaviour under a voluntary vaccination policy can vary substantially depending on interactions between social contact structure, perceived vaccine and disease risks, and the way that individual vaccination decision-making is modelled. PMID- 19476618 TI - Implications of the HIV testing protocol for refusal bias in seroprevalence surveys. AB - BACKGROUND: HIV serosurveys have become important sources of HIV prevalence estimates, but these estimates may be biased because of refusals and other forms of non-response. We investigate the effect of the post-test counseling study protocol on bias due to the refusal to be tested. METHODS: Data come from a nine month prospective study of hospital admissions in Addis Ababa during which patients were approached for an HIV test. Patients had the choice between three consent levels: testing and post-test counseling (including the return of HIV test results), testing without post-test counseling, and total refusal. For all patients, information was collected on basic sociodemographic background characteristics as well as admission diagnosis. The three consent levels are used to mimic refusal bias in serosurveys with different post-test counseling study protocols. We first investigate the covariates of consent for testing. Second, we quantify refusal bias in HIV prevalence estimates using Heckman regression models that account for sample selection. RESULTS: Refusal to be tested positively correlates with admission diagnosis (and thus HIV status), but the magnitude of refusal bias in HIV prevalence surveys depends on the study protocol. Bias is larger when post-test counseling and the return of HIV test results is a prerequisite of study participation (compared to a protocol where test results are not returned to study participants, or, where there is an explicit provision for respondents to forego post-test counseling). We also find that consent for testing increased following the introduction of antiretroviral therapy in Ethiopia. Other covariates of refusal are age (non-linear effect), gender (higher refusal rates in men), marital status (lowest refusal rates in singles), educational status (refusal rate increases with educational attainment), and counselor. CONCLUSION: The protocol for post-test counseling and the return of HIV test results to study participants is an important consideration in HIV prevalence surveys that wish to minimize refusal bias. The availability of ART is likely to reduce refusal rates. PMID- 19476617 TI - The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry. AB - BACKGROUND: Three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Interestingly, CD81 is also required for Plasmodium infection. A major characteristic of tetraspanins is their ability to interact with each other and other transmembrane proteins to build tetraspanin-enriched microdomains (TEM). RESULTS: In our study, we describe a human hepatoma Huh-7 cell clone (Huh-7w7) which has lost CD81 expression and can be infected by HCV when human CD81 (hCD81) or mouse CD81 (mCD81) is ectopically expressed. We took advantage of these permissive cells expressing mCD81 and the previously described MT81/MT81w mAbs to analyze the role of TEM-associated CD81 in HCV infection. Importantly, MT81w antibody, which only recognizes TEM-associated mCD81, did not strongly affect HCV infection. Furthermore, cholesterol depletion, which inhibits HCV infection and reduces total cell surface expression of CD81, did not affect TEM-associated CD81 levels. In addition, sphingomyelinase treatment, which also reduces HCV infection and cell surface expression of total CD81, raised TEM-associated CD81 levels. CONCLUSION: In contrast to Plasmodium infection, our data show that association of CD81 with TEM is not essential for the early steps of HCV life cycle, indicating that these two pathogens, while using the same molecules, invade their host by different mechanisms. PMID- 19476619 TI - Biases in Drosophila melanogaster protein trap screens. AB - BACKGROUND: The ability to localise or follow endogenous proteins in real time in vivo is of tremendous utility for cell biology or systems biology studies. Protein trap screens utilise the random genomic insertion of a transposon-borne artificial reporter exon (e.g. encoding the green fluorescent protein, GFP) into an intron of an endogenous gene to generate a fluorescent fusion protein. Despite recent efforts aimed at achieving comprehensive coverage of the genes encoded in the Drosophila genome, the repertoire of genes that yield protein traps is still small. RESULTS: We analysed the collection of available protein trap lines in Drosophila melanogaster and identified potential biases that are likely to restrict genome coverage in protein trap screens. The protein trap screens investigated here primarily used P-element vectors and thus exhibit some of the same positional biases associated with this transposon that are evident from the comprehensive Drosophila Gene Disruption Project. We further found that protein trap target genes usually exhibit broad and persistent expression during embryonic development, which is likely to facilitate better detection. In addition, we investigated the likely influence of the GFP exon on host protein structure and found that protein trap insertions have a significant bias for exon exon boundaries that encode disordered protein regions. 38.8% of GFP insertions land in disordered protein regions compared with only 23.4% in the case of non trapping P-element insertions landing in coding sequence introns (p < 10(-4)). Interestingly, even in cases where protein domains are predicted, protein trap insertions frequently occur in regions encoding surface exposed areas that are likely to be functionally neutral. Considering the various biases observed, we predict that less than one third of intron-containing genes are likely to be amenable to trapping by the existing methods. CONCLUSION: Our analyses suggest that the utility of P-element vectors for protein trap screens has largely been exhausted, and that approximately 2,800 genes may still be amenable using piggyBac vectors. Thus protein trap strategies based on current approaches are unlikely to offer true genome-wide coverage. We suggest that either transposons with reduced insertion bias or recombineering-based targeting techniques will be required for comprehensive genome coverage in Drosophila. PMID- 19476620 TI - Analyzing miRNA co-expression networks to explore TF-miRNA regulation. AB - BACKGROUND: Current microRNA (miRNA) research in progress has engendered rapid accumulation of expression data evolving from microarray experiments. Such experiments are generally performed over different tissues belonging to a specific species of metazoan. For disease diagnosis, microarray probes are also prepared with tissues taken from similar organs of different candidates of an organism. Expression data of miRNAs are frequently mapped to co-expression networks to study the functions of miRNAs, their regulation on genes and to explore the complex regulatory network that might exist between Transcription Factors (TFs), genes and miRNAs. These directions of research relating miRNAs are still not fully explored, and therefore, construction of reliable and compatible methods for mining miRNA co-expression networks has become an emerging area. This paper introduces a novel method for mining the miRNA co-expression networks in order to obtain co-expressed miRNAs under the hypothesis that these might be regulated by common TFs. RESULTS: Three co-expression networks, configured from one patient-specific, one tissue-specific and a stem cell-based miRNA expression data, are studied for analyzing the proposed methodology. A novel compactness measure is introduced. The results establish the statistical significance of the sets of miRNAs evolved and the efficacy of the self-pruning phase employed by the proposed method. All these datasets yield similar network patterns and produce coherent groups of miRNAs. The existence of common TFs, regulating these groups of miRNAs, is empirically tested. The results found are very promising. A novel visual validation method is also proposed that reflects the homogeneity as well as statistical properties of the grouped miRNAs. This visual validation method provides a promising and statistically significant graphical tool for expression analysis. CONCLUSION: A heuristic mining methodology that resembles a clustering motivation is proposed in this paper. However, there remains a basic difference between the mining method and a clustering approach. The heuristic approach can produce priority modules (PM) from an miRNA co-expression network, by employing a self-pruning phase, which are analyzed for statistical and biological significance. The mining algorithm minimizes the space/time complexity of the analysis, and also handles noise in the data. In addition, the mining method reveals promising results in the unsupervised analysis of TF-miRNA regulation. PMID- 19476622 TI - The specificity and the development of social-emotional competence in a multi ethnic-classroom. AB - BACKGROUND: Ethnic diversity in schools increases due to globalization. Thus, the children's social-emotional competence development must be considered in the context of a multi-ethnic classroom. METHODS: In this study, the social-emotional competence of 65 Asian-American and Latin-American children was observed at the beginning and the end of their kindergarten year. RESULTS: Initially, significant differences existed among these ethnic groups in respect to moral reasoning. Furthermore, the male children showed more dysregulated aggression but the female children implemented more moral reasoning than their male counterparts. These ethnic specificities did not disappear over the course of the year. In addition, a significant change in avoidance strategies as well as expressed emotions in the narrative took place over the course of one year. CONCLUSION: Ethnic specificity in social-emotional competence does exist independent of gender at the beginning as well as at the end of the kindergarten year in a multi-ethnic kindergarten classroom. PMID- 19476621 TI - Progesterone receptor does not improve the performance and test effectiveness of the conventional 3-marker panel, consisting of estrogen receptor, vimentin and carcinoembryonic antigen in distinguishing between primary endocervical and endometrial adenocarcinomas in a tissue microarray extension study. AB - OBJECTIVE: Endocervical adenocarcinomas (ECA) and endometrial adenocarcinomas (EMA) are uterine malignancies that have differing biological behaviors. The choice of an appropriate therapeutic plan rests on the tumor's site of origin. In this study, we propose to evaluate whether PR adds value to the performance and test effectiveness of the conventional 3-marker (ER/Vim/CEA) panel in distinguishing between primary ECA and EMA. METHODS: A tissue microarray was constructed using paraffin-embedded, formalin-fixed tissues from 38 hysterectomy specimens, including 14 ECA and 24 EMA. Tissue microarray (TMA) sections were immunostained with 4 antibodies, using the avidin-biotin complex (ABC) method for antigen visualization. The staining intensity and extent of the immunohistochemical (IHC) reactions were appraised using a semi-quantitative scoring system. RESULTS: The three markers (ER, Vim and CEA) and their respective panel expressions showed statistically significant (p < 0.05) frequency differences between ECA and EMA tumors. Although the additional ancillary PR marker also revealed a significant frequency difference (p < 0.05) between ECA and EMA tumors, it did not demonstrate any supplementary benefit to the 3-marker panel. CONCLUSION: According to our data, when histomorphological and clinical doubt exists as to the primary site of origin, we recommend that the conventional 3-marker (ER/Vim/CEA) panel is easier, sufficient and appropriate to use in distinguishing between primary ECA and EMA. Although the 4-marker panel containing PR also reveals statistically significant results, the PR-marker offers no supplemental benefit to the pre-existing 3-marker (ER/Vim/CEA) panel in the diagnostic distinction between ECA and EMA. PMID- 19476624 TI - DDX11L: a novel transcript family emerging from human subtelomeric regions. AB - BACKGROUND: The subtelomeric regions of human chromosomes exhibit an extraordinary plasticity. To date, due to the high GC content and to the presence of telomeric repeats, the subtelomeric sequences are underrepresented in the genomic libraries and consequently their sequences are incomplete in the finished human genome sequence, and still much remains to be learned about subtelomere organization, evolution and function. Indeed, only in recent years, several studies have disclosed, within human subtelomeres, novel gene family members. RESULTS: During a project aimed to analyze genes located in the telomeric region of the long arm of the human X chromosome, we have identified a novel transcript family, DDX11L, members of which map to 1pter, 2q13/14.1, 2qter, 3qter, 6pter, 9pter/9qter, 11pter, 12pter, 15qter, 16pter, 17pter, 19pter, 20pter/20qter, Xpter/Xqter and Yqter. Furthermore, we partially sequenced the underrepresented subtelomeres of human chromosomes showing a common evolutionary origin. CONCLUSION: Our data indicate that an ancestral gene, originated as a rearranged portion of the primate DDX11 gene, and propagated along many subtelomeric locations, is emerging within subtelomeres of human chromosomes, defining a novel gene family. These findings support the possibility that the high plasticity of these regions, sites of DNA exchange among different chromosomes, could trigger the emergence of new genes. PMID- 19476623 TI - Cemented versus non-cemented hemiarthroplasty of the hip as a treatment for a displaced femoral neck fracture: design of a randomised controlled trial. AB - BACKGROUND: A discussion is ongoing whether displaced femoral neck fractures in elderly patients should be treated with a non-cemented or a cemented hemiarthroplasty. A recent Cochrane analysis stresses the importance of further research into the relative merits of these techniques. We hypothesise that non cemented hemiarthroplasty will result in at least the same technical-functional outcome and complication rate, with a shorter operation time. METHODS AND DESIGN: A randomised controlled multicentre trial will be performed.The study population consists of 200 patients of 70 years and older. Patients with a displaced femoral neck fracture will be allocated randomly to have a cemented or a non-cemented hemiarthroplasty. Data will be collected preoperatively, immediately postoperatively, and 6 weeks, 3 months and 1 year postoperatively.The main outcome measures of this study are technical-functional results of the hemiarthroplasty, duration of surgery, complications, and mid-thigh pain. Secondary outcome measures are living conditions at final follow up, self reported health-related quality of life, and radiological evaluation of the hemiarthroplasty. CONCLUSION: A recent Cochrane analysis did not find arguments in favour of either non-cemented or cemented hemiarthroplasty. The forthcoming trial will compare treatment for a displaced femoral neck fracture by cemented versus non-cemented hemiarthroplasty. Our results will be published as soon as they become available. TRIAL REGISTRATION: Trial Registration Number NTR1508. PMID- 19476625 TI - Serum high mobility group box-1 (HMGB1) is closely associated with the clinical and pathologic features of gastric cancer. AB - BACKGROUND: High mobility group box-1 (HMGB1) is a newly recognized factor regulating cancer cell tumorigenesis, expansion and invasion. We investigated the correlation between the serum HMGB1 levels and the clinical and pathologic features of gastric cancer and evaluated the validity of HMGB1 as a potential biomarker for the early diagnosis of gastric cancer. METHODS: A total of 227 subjects were classified into 5 disease groups according to the 'gastritis dysplasia-carcinoma' sequence of gastric carcinogenesis and their serum levels of HMGB1 were analyzed by an enzyme-linked immunosorbent assay (ELISA) method. Clinical parameters, International Union Against Cancer (UICC) TNM stage, cancer size, differentiation or lymphatic invasion, vascular or perineural invasion and prognosis were used as analysis variables. RESULTS: The serum HMGB1 levels were significantly different among disease groups (ANOVA, p < 0.05) and HMGB1 levels tended to increase according to the progression of gastric carcinogenesis. Serum HMGB1 levels were significantly associated with depth of invasion, lymph node metastasis, tumor size, and poor prognosis (p < 0.05). However, HMGB1 levels were not associated with patient gender or age, differentiation of tumor cells, or lymphatic, vascular and perineural invasion, or the existence of distant metastasis in advanced cancer (p > 0.05). The sensitivity and specificity of serum HMGB1 was 71% and 67% (cut-off value of 5 ng/ml) for the diagnosis of early gastric cancer, and 70% and 64% (cut-off value of 4 ng/ml) for the diagnosis of high-risk lesions, respectively. These values were greater than those for carcinoembryonic antigen (CEA) (30-40% of sensitivity). CONCLUSION: HMGB1 appears to be a useful serological biomarker for early diagnosis as well as evaluating the tumorigenesis, stage, and prognosis of gastric cancer. PMID- 19476628 TI - Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results. AB - BACKGROUND: In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. METHODS: Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. RESULTS: By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. CONCLUSION: Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging. PMID- 19476626 TI - Modeling of solvent-dependent conformational transitions in Burkholderia cepacia lipase. AB - BACKGROUND: The characteristic of most lipases is the interfacial activation at a lipid interface or in non-polar solvents. Interfacial activation is linked to a large conformational change of a lid, from a closed to an open conformation which makes the active site accessible for substrates. While for many lipases crystal structures of the closed and open conformation have been determined, the pathway of the conformational transition and possible bottlenecks are unknown. Therefore, molecular dynamics simulations of a closed homology model and an open crystal structure of Burkholderia cepacia lipase in water and toluene were performed to investigate the influence of solvents on structure, dynamics, and the conformational transition of the lid. RESULTS: The conformational transition of B. cepacia lipase was dependent on the solvent. In simulations of closed B. cepacia lipase in water no conformational transition was observed, while in three independent simulations of the closed lipase in toluene the lid gradually opened during the first 10-15 ns. The pathway of conformational transition was accessible and a barrier was identified, where a helix prevented the lid from opening to the completely open conformation. The open structure in toluene was stabilized by the formation of hydrogen bonds.In simulations of open lipase in water, the lid closed slowly during 30 ns nearly reaching its position in the closed crystal structure, while a further lid opening compared to the crystal structure was observed in toluene. While the helical structure of the lid was intact during opening in toluene, it partially unfolded upon closing in water. The closing of the lid in water was also observed, when with eight intermediate structures between the closed and the open conformation as derived from the simulations in toluene were taken as starting structures. A hydrophobic beta hairpin was moving away from the lid in all simulations in water, which was not observed in simulations in toluene. The conformational transition of the lid was not correlated to the motions of the beta-hairpin structure. CONCLUSION: Conformational transitions between the experimentally observed closed and open conformation of the lid were observed by multiple molecular dynamics simulations of B. cepacia lipase. Transitions in both directions occurred without applying restraints or external forces. The opening and closing were driven by the solvent and independent of a bound substrate molecule. PMID- 19476627 TI - High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN gamma release assay among HIV-infected individuals in BCG-vaccinated area. AB - BACKGROUND: An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT)-based IFN-gamma release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG)-vaccinated area. A total of 100 HIV infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-gamma release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-gamma response. Tuberculin skin test (TST) was performed for all recruited subjects. RESULTS: The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32), group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46) and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22). In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST <5 mm were 50% (16/32) and 41.3% (19/46), respectively. Individuals in group HIV+ATB and HIV+LTB with CD4+ T cells <500/microl, T-SPOT.TB showed a higher sensitivity than TST (64.5% vs. 22.6% and 62.2% vs. 29.7%, respectively, both P < 0.0001). In addition, the sensitivity of T-SPOT.TB assay in group HIV+ATB increased to >85% in patients with TB treatment for less than 1 month and CD4+ T cells > or = 200/microl, while for patients treated for more than 3 months and CD4+ T cells <200/microl, the sensitivity was decreased to only 33.3%. Furthermore, the results could be generated by T-SPOT.TB assay within 24 hours, which was more rapid than TST with 48-72 hours. CONCLUSION: ELISPOT-based IFN-gamma release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China. PMID- 19476630 TI - Exposure to bile influences biofilm formation by Listeria monocytogenes. AB - In the present study we demonstrate that the initial attachment of Listeria monocytogenes cells to plastic surfaces was significantly increased by growth in the presence of bile. Improved biofilm formation was confirmed by crystal violet staining, microscopy and bioluminescence detection of a luciferase-tagged strain. Enhanced biofilm formation in response to bile may influence the ability of L. monocytogenes to form biofilms in vivo during infection and may contribute to survival of this important pathogen in the human gastrointestinal tract and gallbladder. PMID- 19476629 TI - Do serum biomarkers really measure breast cancer? AB - BACKGROUND: Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. METHODS: This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave one-out cross-validation (LOOCV) and receiver operating characteristic (ROC) curve analysis. RESULTS: The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 +/- 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 +/- 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 +/- 0.06). The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. CONCLUSION: Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy. PMID- 19476631 TI - Women with endometriosis improved their peripheral antioxidant markers after the application of a high antioxidant diet. AB - BACKGROUND: Oxidative stress has been identified in the peritoneal fluid and peripheral blood of women with endometriosis. However, there is little information on the antioxidant intake for this group of women. The objectives of this work were 1) to compare the antioxidant intake among women with and without endometriosis and 2) to design and apply a high antioxidant diet to evaluate its capacity to reduce oxidative stress markers and improve antioxidant markers in the peripheral blood of women with endometriosis. METHODS: Women with (WEN, n = 83) and without endometriosis (WWE, n = 80) were interviewed using a Food Frequency Questionnaire to compare their antioxidant intake (of vitamins and minerals). Then, the WEN participated in the application of a control (n = 35) and high antioxidant diet (n = 37) for four months. The high antioxidant diet (HAD) guaranteed the intake of 150% of the suggested daily intake of vitamin A (1050 microg retinol equivalents), 660% of the recommended daily intake (RDI) of vitamin C (500 mg) and 133% of the RDI of vitamin E (20 mg). Oxidative stress and antioxidant markers (vitamins and antioxidant enzymatic activity) were determined in plasma every month. RESULTS: Comparison of antioxidant intake between WWE and WEN showed a lower intake of vitamins A, C, E, zinc, and copper by WEN (p < 0.05, Mann Whitney Rank test). The selenium intake was not statistically different between groups. During the study, the comparison of the 24-hour recalls between groups showed a higher intake of the three vitamins in the HAD group. An increase in the vitamin concentrations (serum retinol, alpha-tocopherol, leukocyte and plasma ascorbate) and antioxidant enzyme activity (superoxide dismutase and glutathione peroxidase) as well as a decrease in oxidative stress markers (malondialdehyde and lipid hydroperoxides) were observed in the HAD group after two months of intervention. These phenomena were not observed in the control group. CONCLUSION: WEN had a lower intake of antioxidants in comparison to WWE. Peripheral oxidative stress markers diminished, and antioxidant markers were enhanced, in WEN after the application of the HAD. PMID- 19476632 TI - Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress. AB - BACKGROUND: Mitochondrial proteins are central to various metabolic activities and are key regulators of apoptosis. Disturbance of mitochondrial proteins is therefore often associated with disease. Large scale protein data are required to capture the mitochondrial protein levels and mass spectrometry based proteomics is suitable for generating such data. To study the relative quantities of mitochondrial proteins in cells from cultivated human skin fibroblasts we applied a proteomic method based on nanoLC-MS/MS analysis of iTRAQ-labeled peptides. RESULTS: When fibroblast cultures were exposed to mild metabolic stress - by cultivation in galactose medium- the amount of mitochondria appeared to be maintained whereas the levels of individual proteins were altered. Proteins of respiratory chain complex I and IV were increased together with NAD+-dependent isocitrate dehydrogenase of the citric acid cycle illustrating cellular strategies to cope with altered energy metabolism. Furthermore, quantitative protein data, with a median standard error below 6%, were obtained for the following mitochondrial pathways: fatty acid oxidation, citric acid cycle, respiratory chain, antioxidant systems, amino acid metabolism, mitochondrial translation, protein quality control, mitochondrial morphology and apoptosis. CONCLUSION: The robust analytical platform in combination with a well-defined compendium of mitochondrial proteins allowed quantification of single proteins as well as mapping of entire pathways. This enabled characterization of the interplay between metabolism and stress response in human cells exposed to mild stress. PMID- 19476633 TI - The PhoBR two-component system regulates antibiotic biosynthesis in Serratia in response to phosphate. AB - BACKGROUND: Secondary metabolism in Serratia sp. ATCC 39006 (Serratia 39006) is controlled via a complex network of regulators, including a LuxIR-type (SmaIR) quorum sensing (QS) system. Here we investigate the molecular mechanism by which phosphate limitation controls biosynthesis of two antibiotic secondary metabolites, prodigiosin and carbapenem, in Serratia 39006. RESULTS: We demonstrate that a mutation in the high affinity phosphate transporter pstSCAB phoU, believed to mimic low phosphate conditions, causes upregulation of secondary metabolism and QS in Serratia 39006, via the PhoBR two-component system. Phosphate limitation also activated secondary metabolism and QS in Serratia 39006. In addition, a pstS mutation resulted in upregulation of rap. Rap, a putative SlyA/MarR-family transcriptional regulator, shares similarity with the global regulator RovA (regulator of virulence) from Yersina spp. and is an activator of secondary metabolism in Serratia 39006. We demonstrate that expression of rap, pigA-O (encoding the prodigiosin biosynthetic operon) and smaI are controlled via PhoBR in Serratia 39006. CONCLUSION: Phosphate limitation regulates secondary metabolism in Serratia 39006 via multiple inter-linked pathways, incorporating transcriptional control mediated by three important global regulators, PhoB, SmaR and Rap. PMID- 19476635 TI - Expressions of IGFBP-5, cFLIP in cervical intraepithelial neoplasia, cervical carcinoma and their clinical significances: a molecular pathology. AB - BACKGROUND: Insulin-like growth factor binding protein (IGFBPs) have been as potential tumor suppressors in the occurrence and development of tumors. Cellular Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE)-like inhibitory protein (cFLIP) contains a death effect domain (DED), which blocks death receptor pathway and inhibits apoptosis. METHODS: We collected normal cervical tissues from 28 subjects, CIN samples from 37 patients, and cervical cancer tissues from 40 patients. In these samples, we then measured the expression levels of IGFBP-5 and cFLIP via RT-PCR and immunohistochemistry, and we detected the presence of high-risk HPV by Hybrid capture II assays in cervical secretions provided by the subjects. RESULTS: significant differences in the expression of IGFBP-5 protein among the normal, CIN, and CC tissues (P < 0.05). The highest expression of IGFBP-5 protein was found in CIN stage II and III tissues, whereas the expression of IGFBP-5 in CC samples was decreased relative to controls. The expression level was affected by factors such as clinical stage, pathological differentiation, and lymph node metastasis. Relative to the controls, IGFBP-5 mRNA content was higher in the CC group and lower in the CIN group (P < 0.05). No expression of cFLIP protein or mRNA was detected in normal cervical tissues. However, the degree of pathological changes correlated with increasing expression of cFLIP protein and mRNA, and significant differences were therefore detected between groups (P < 0.05). The HPV infection rates in the CIN and CC groups were much higher than in the normal group (P < 0.05). CONCLUSION: IGFBP-5 expression is up-regulated in response to progression of CIN and down regulated in invasive cervical carcinoma. Detection of IGFBP-5 and cFLIP expression levels, may prove particularly useful for diagnosing and differentiating CIN and CC. PMID- 19476634 TI - Sample size calculation for microarray experiments with blocked one-way design. AB - BACKGROUND: One of the main objectives of microarray analysis is to identify differentially expressed genes for different types of cells or treatments. Many statistical methods have been proposed to assess the treatment effects in microarray experiments. RESULTS: In this paper, we consider discovery of the genes that are differentially expressed among K (> 2) treatments when each set of K arrays consists of a block. In this case, the array data among K treatments tend to be correlated because of block effect. We propose to use the blocked one way ANOVA F-statistic to test if each gene is differentially expressed among K treatments. The marginal p-values are calculated using a permutation method accounting for the block effect, adjusting for the multiplicity of the testing procedure by controlling the false discovery rate (FDR). We propose a sample size calculation method for microarray experiments with a blocked one-way design. With FDR level and effect sizes of genes specified, our formula provides a sample size for a given number of true discoveries. CONCLUSION: The calculated sample size is shown via simulations to provide an accurate number of true discoveries while controlling the FDR at the desired level. PMID- 19476636 TI - Protein synthesis is essential not only for consolidation but also for maintenance and post-retrieval reconsolidation of acrobatic motor skill in rats. AB - It has been reported that consolidation of motor skill, a type of non-declarative memories, requires protein synthesis, as hippocampus-dependent declarative memory does. However, little is known about the importance of protein synthesis in maintenance and especially post-retrieval reconsolidation of acrobatic motor skill. Here, we show that protein synthesis is essential not only for the consolidation but also for the maintenance and reconsolidation of a rotarod running skill. Intra-ventricle infusion of the protein synthesis inhibitor anisomycin 0 h but not 2 h post-training caused a severe deficit in the acquisition of the rotarod-running skill. Protein synthesis inhibition (PSI) also caused a deficit in the maintenance of the rotarod-running skill, as well-trained rats demonstrated a deficit in the rotarod-running performance upon treatment with anisomycin. Similarly, PSI impaired the post-retrieval reconsolidation of the rotarod-running skill: well-trained rats treated with anisomycin 0 h but not 0.5, 2 and 4 h after the task performance exhibited amnesia for the running skill later on. Interestingly, rats treated with anisomycin 6 and 12 h post-retrieval exhibited amnesia for the running skill. Thus, protein synthesis is essential not only for the consolidation but also for the maintenance and post-retrieval reconsolidation of rotarod-running acrobatic motor skill. PMID- 19476637 TI - A pilot study evaluating use of a computer-assisted neurorehabilitation platform for upper-extremity stroke assessment. AB - BACKGROUND: There is a need to develop cost-effective, sensitive stroke assessment instruments. One approach is examining kinematic measures derived from goal-directed tasks, which can potentially be sensitive to the subtle changes in the stroke rehabilitation process. This paper presents the findings from a pilot study that uses a computer-assisted neurorehabilitation platform, interfaced with a conventional force-reflecting joystick, to examine the assessment capability of the system by various types of goal-directed tasks. METHODS: Both stroke subjects with hemiparesis and able-bodied subjects used the force-reflecting joystick to complete a suite of goal-directed tasks under various task settings. Kinematic metrics, developed for specific types of goal-directed tasks, were used to assess various aspects of upper-extremity motor performance across subjects. RESULTS: A number of metrics based on kinematic performance were able to differentiate subjects with different impairment levels, with metrics associated with accuracy, steadiness and speed consistency showing the best capability. Significant differences were also shown on these metrics between various force field settings. CONCLUSION: The results support the potential of using UniTherapy software with a conventional joystick system as an upper-extremity assessment instrument. We demonstrated the ability of using various types of goal-directed tasks to distinguish between subjects with different impairment levels. In addition, we were able to show that different force fields have a significant effect on the performance across subjects with different impairment levels in the trajectory tracking task. These results provide motivation for studies with a larger sample size that can more completely span the impairment space, and can use insights presented here to refine considerations of various task settings so as to generalize and extend our conclusions. PMID- 19476638 TI - A pentaplex PCR assay for the rapid detection of methicillin-resistant Staphylococcus aureus and Panton-Valentine Leucocidin. AB - BACKGROUND: Staphylococcus aureus is a major human pathogen, especially methicillin-resistant S. aureus (MRSA), which causes a wide range of hospital and community-acquired infections worldwide. Conventional testing for detection of MRSA takes 2-5 days to yield complete information of the organism and its antibiotic sensitivity pattern. RESULTS: The present study focused on the development of a pentaplex PCR assay for the rapid detection of MRSA. The assay simultaneously detected five genes, namely 16S rRNA of the Staphylococcus genus, femA of S. aureus, mecA that encodes methicillin resistance, lukS that encodes production of Panton-Valentine leukocidin (PVL), a necrotizing cytotoxin, and one internal control. Specific primer pairs were successfully designed and simultaneously amplified the targeted genes. The analytical sensitivity and specificity of the pentaplex PCR assay was evaluated by comparing it with the conventional method. The analytical sensitivity of the pentaplex PCR at the DNA level was found to be 10 ng DNA. The analytical specificity was evaluated with 34 reference staphylococci and non-staphylococcal strains and was found to be 100%. The diagnostic evaluation of MRSA carried out using 230 clinical isolates, showed 97.6% of sensitivity, 99.3% of specificity, 98.8% of positive predictive value and 98.6% of negative predictive value compared to the conventional method. The presence of an internal control in the pentaplex PCR assay is important to exclude false-negative cases. CONCLUSION: The pentaplex PCR assay developed was rapid and gave results within 4 h, which is essential for the identification of Staphylococcus spp., virulence and their resistance to methicillin. Our PCR assay may be used as an effective surveillance tool to survey the prevalence of MRSA and PVL-producing strains in hospitals and the community. PMID- 19476639 TI - Computational investigation of epithelial cell dynamic phenotype in vitro. AB - BACKGROUND: When grown in three-dimensional (3D) cultures, epithelial cells typically form cystic organoids that recapitulate cardinal features of in vivo epithelial structures. Characterizing essential cell actions and their roles, which constitute the system's dynamic phenotype, is critical to gaining deeper insight into the cystogenesis phenomena. METHODS: Starting with an earlier in silico epithelial analogue (ISEA1) that validated for several Madin-Darby canine kidney (MDCK) epithelial cell culture attributes, we built a revised analogue (ISEA2) to increase overlap between analogue and cell culture traits. Both analogues used agent-based, discrete event methods. A set of axioms determined ISEA behaviors; together, they specified the analogue's operating principles. A new experimentation framework enabled tracking relative axiom use and roles during simulated cystogenesis along with establishment of the consequences of their disruption. RESULTS: ISEA2 consistently produced convex cystic structures in a simulated embedded culture. Axiom use measures provided detailed descriptions of the analogue's dynamic phenotype. Dysregulating key cell death and division axioms led to disorganized structures. Adhering to either axiom less than 80% of the time caused ISEA1 to form easily identified morphological changes. ISEA2 was more robust to identical dysregulation. Both dysregulated analogues exhibited characteristics that resembled those associated with an in vitro model of early glandular epithelial cancer. CONCLUSION: We documented the causal chains of events, and their relative roles, responsible for simulated cystogenesis. The results stand as an early hypothesis--a theory--of how individual MDCK cell actions give rise to consistently roundish, cystic organoids. PMID- 19476640 TI - Associations between cardiorespiratory fitness and health-related quality of life. AB - BACKGROUND: There is limited data examining the association between cardiorespiratory fitness (CRF) and health related quality of life (HRQOL) in healthy young adults. We examined the association between CRF and the HRQOL Physical Component Summary (PCS) and Mental Component Summary (MCS) scores in apparently healthy males in the United States Navy. METHODS: A total of 709 males (18-49 yr) performed a submaximal exercise test and HRQOL assessment (SF-12v2) between 2004-2006. CRF level was classified into fourths depending on age distribution with the lowest fitness quartile serving as the referent group. PCS and MCS scores >or= 50 were defined as above the norm. Logistic regression was used to obtain odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The age-standardized prevalence of above the norm scores was lowest in the referent CRF quartile, PCS 56.6% and MCS 45.1%. After adjusting for age, systolic blood pressure, body mass index, smoking habit, alcohol habit and using the lowest CRF group as the reference, the OR (95% CI) for PCS scores above the norm across the fitness quartiles (P < 0.003 for trend) were 1.51(0.94-2.41), 2.24(1.29-3.90), and 2.44 (1.30-4.57); For MCS the OR (95% CI) were across the fitness quartiles (P trend < 0.001) 2.03(1.27-3.24), 4.53(2.60-7.90), 3.59(1.95-6.60). CONCLUSION: Among males in the United States Navy relative higher levels of CRF are associated with higher levels of HRQOL. PMID- 19476643 TI - The WHO checklist: a global tool to prevent errors in surgery. AB - In this article, we welcome the adoption of the WHO surgical checklist to prevent errors in surgical practice. We highlight the scale of the problem and discuss the adoption of this tool in the UK. PMID- 19476641 TI - Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation. AB - BACKGROUND: Cannabinoid receptor type 2 (CBR2) inhibits microglial reactivity through a molecular mechanism yet to be elucidated. We hypothesized that CBR2 activation induces an anti-inflammatory phenotype in microglia by inhibiting extracellular signal-regulated kinase (ERK) pathway, via mitogen-activated protein kinase-phosphatase (MKP) induction. MKPs regulate mitogen activated protein kinases, but their role in the modulation of microglial phenotype is not fully understood. RESULTS: JWH015 (a CBR2 agonist) increased MKP-1 and MKP-3 expression, which in turn reduced p-ERK1/2 in LPS-stimulated primary microglia. These effects resulted in a significant reduction of tumor necrosis factor-alpha (TNF) expression and microglial migration. We confirmed the causative link of these findings by using MKP inhibitors. We found that the selective inhibition of MKP-1 by Ro-31-8220 and PSI2106, did not affect p-ERK expression in LPS+JWH015 treated microglia. However, the inhibition of both MKP-1 and MKP-3 by triptolide induced an increase in p-ERK expression and in microglial migration using LPS+JWH015-treated microglia. CONCLUSION: Our results uncover a cellular microglial pathway triggered by CBR2 activation. These data suggest that the reduction of pro-inflammatory factors and microglial migration via MKP-3 induction is part of the mechanism of action of CBR2 agonists. These findings may have clinical implications for further drug development. PMID- 19476642 TI - Early-onset breast cancer in a Lebanese family with Lynch syndrome due to MSH2 gene mutation. AB - BACKGROUND: There are still controversies about the integration of breast cancer as a part of the disease spectrum in Lynch syndrome. METHODS: A regular follow-up of a Lebanese pedigree with Lynch syndrome due to a point mutation of MSH2 gene at the splice donor site of intron 3 started in 1996. RESULTS: A 26-year-old pregnant woman, mutation carrier, developed an aggressive breast cancer, refractory to standard chemotherapy regimens. The microsatellite analysis of the tumor showed an unstable pattern for markers BAT25 and BAT26. The immunohistochemical staining was negative for MSH2 and MSH6 and normal for MLH1 and PMS6 enzymes. CONCLUSION: The segregation of the mutation with the disease phenotype and these results suggest that MSH2 inactivation may be involved in the accelerated breast carcinogenesis and might be considered in the cancer screening program. PMID- 19476644 TI - Is adiponectin associated with acute myocardial infarction in Iranian non obese patients? AB - BACKGROUND: Adiponectin is an adipose tissue-derived mediator with significant anti-atherogenic properties. A few studies were done in acute phase of myocardial infarction especially in non obese patients. We design a study to investigate the association between adiponectin concentration and acute phase of myocardial infarction in non obese patients. METHODS: This case-control study was done in Paymaneah Hospital (Jahrom, Iran) from Feb 2007 to May 2008. Plasma adiponectin levels were measured in 43 patients with AMI (mean age: 62.7 +/- 13.3 years, male: 67.4%) at the first 24 hours of admission and 43 normal controls (mean age: 62.1 +/- 12.3 years, male: 55.8%) matched for age, sex and other CAD risk factors. RESULTS: Adiponectin levels in patients with AMI (3.36 microg/mL) were significantly lower than that of the control group (5.03 microg/mL) (p < 0.0001). Lower adiponectin were independently associated with higher risk of AMI (odds ratio = 8.97; 95% CIs: 2.3-34.5; p = 0.001). Adiponectin levels negatively correlated with triglyceride (r = -0.46, p = 0.002) and total cholesterol (r = 0.32, p = 0.03) in the case group and with body mass index (BMI) in control subjects. CONCLUSION: The present study showed that adiponectin was associated with AMI in non obese patients but it is not related to sex, age and other CAD risk factors. PMID- 19476645 TI - No evidence of BRCA2 mutations in chromosome 13q-linked Utah high-risk prostate cancer pedigrees. AB - BACKGROUND: Germline mutations in the BRCA2 gene have been suggested to account for about 5% of familial prostate cancer; mutations have been reported in 2% of early onset (i.e., 65 (n = 53) who had been discharged to the community following an acute hospital admission underwent telephone administration of the FAI and EQ-5D instruments seven days prior to attending a hospital outpatient appointment where they completed a face-to-face administration of these instruments. RESULTS: Overall, 40 subjects' datasets were complete for both assessments and included in analysis. The FAI items had high levels of agreement between the two modes of administration (item kappa's ranged 0.73 to 1.00) as did the EQ-5D (item kappa's ranged 0.67-0.83). For the FAI, EQ-5D VAS and EQ-5D utility score, intraclass correlation coefficients were 0.94, 0.58 and 0.82 respectively with paired t tests indicating no significant systematic difference (p = 0.100, p = 0.690 and p = 0.290 respectively). CONCLUSION: Telephone administration of the FAI and EQ-5D instruments provides comparable results to face-to-face administration amongst older adults deemed to have cognitive functioning intact at a basic level, indicating that this is a suitable alternate approach for collection of this information. PMID- 19476657 TI - Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis. AB - BACKGROUND: In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. Tbx1, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. Tbx1 is expressed in the otic epithelium and adjacent periotic mesenchyme (POM), and both of these domains are required for inner ear formation. To study the function of Tbx1 in the POM, we have conditionally inactivated Tbx1 in the mesoderm while keeping expression in the otic vesicle intact. RESULTS: Conditional mutants (TCre-KO) displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that Tbx1 expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker Brn4 was also lost in the TCre-KO. Brn4-;Tbx1+/-embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA) catabolizing genes was examined in both mutants. Cyp26a1 expression was altered in the TCre-KO, while Cyp26c1 showed reduced expression in both TCre-KO and Brn4-;Tbx1+/- embryos. CONCLUSION: These results indicate that Tbx1 expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity. PMID- 19476658 TI - Diagnostic problems with parasitic and non-parasitic splenic cysts. AB - BACKGROUND: The splenic cysts constitute a very rare clinical entity. They may occur secondary to trauma or even being more seldom due to parasitic infestations, mainly caused by ecchinocccus granulosus. Literature lacks a defined concencus including the treatment plans and follow up strategies, nor long term results of the patients. In the current study, we aimed to evaluate the diagnosis, management of patients with parasitic and non-parasitic splenic cysts together with their long term follow up progresses. METHODS: Twenty-four patients with splenic cysts have undergone surgery in our department over the last 9 years. Data from eighteen of the twenty-four patients were collected prospectively, while data from six were retrospectively collected. All patients were assessed in terms of age, gender, hospital stay, preoperative diagnosis, additional disease, serology, ultrasonography, computed tomography (CT), cyst recurrences and treatment. RESULTS: In this study, the majority of patients presented with abdominal discomfort and palpable swelling in the left hypochondrium. All patients were operated on electively. The patients included 14 female and 10 male patients, with a mean age of 44.77 years (range 20-62). Splenic hydatid cysts were present in 16 patients, one of whom also had liver hydatid cysts (6.25%). Four other patients were operated on for a simple cyst (16%) two patients for an epithelial cyst, and the last two for splenic lymphangioma. Of the 16 patients diagnosed as having splenic hydatit cysts, 11 (68.7%) were correctly diagnosed. Only two of these patients were administered benzimidazole therapy pre-operatively because of the risk of multicystic disease The mean follow-up period was 64 months (6-108). There were no recurrences of splenic cysts. CONCLUSION: Surgeons should keep in mind the possibility of a parasitic cyst when no definitive alternative diagnosis can be made. In the treatment of splenic hydatidosis, benzimidazole therapy is not necessary, although it is crucial to perform splenectomy without rupturing and spilling the cysts. PMID- 19476660 TI - The political undertones of building national health research systems- reflections from The Gambia. AB - In developing countries building national health research systems is a movement similar to a political leadership contest. Increasingly, political campaigns to select leaders depend less on ideologies and political messages and more on promising change that will promptly improve the quality of life of the voters. In this process the benefits and risks of every action and statement made by the candidates are carefully assessed.Approaches currently promoted to strengthen health research within ministries of health in developing countries place emphasis on implementing logical steps towards building national health research systems including developing a national health research policy and strategic plan, conducting a situational analysis of research in the country, setting a national health research agenda, establishing research ethics and scientific committees, and building human and institutional capacity for health research management and conduct. Although these processes have successfully improved the standards of health research in some settings, many developing countries struggle to get the process going. One reason is that this approach does not deal with basic questions posed within a ministry of health, namely, "What is the political benefit of the ministry assuming control of the process?" and "What are the political implications for the ministry if another institution spearheads the process?"Seen from the perspective of non-governmental organizations, academic institutions and donors trying to support the processes of strengthening national health research systems, one of the foremost activities that needs to be undertaken is to analyze the political context of national health research and, on that basis, plan and implement appropriate political health research advocacy initiatives. This includes the development of explicit messages on the political benefits to the leadership in the ministry of health of their role in the conduct, management and dissemination of health research within the country. Civil society organizations, with links to both government and non-governmental organizations, are well placed to play the role of advocates.It is only through broad and active participation of stakeholders that the process of developing effective and sustainable national health research systems will truly become a national movement inspired, led and sustained by ministries of health. PMID- 19476659 TI - The contribution of childhood circumstances, current circumstances and health behaviour to educational health differences in early adulthood. AB - BACKGROUND: The life course approach emphasises the contribution of circumstances in childhood and youth to adult health inequalities. However, there is still a lot to know of the contribution of living conditions in childhood and youth to adult health inequalities and how later environmental and behavioural factors are connected with the effects of earlier circumstances. This study aims to assess a) how much childhood circumstances, current circumstances and health behaviour contribute to educational health differences and b) to which extent the effect of childhood circumstances on educational health differences is shared with the effects of later living conditions and health behaviour in young adults. METHODS: The data derived from the Health 2000 Survey represent the Finnish young adults aged 18-29 in 2000. The analyses were carried out on 68% (n = 1282) of the sample (N = 1894). The cross-sectional data based on interviews and questionnaires include retrospective information on childhood circumstances. The outcome measure was poor self-rated health. RESULTS: Poor self-rated health was much more common among subjects with primary education only than among those in the highest educational category (OR 4.69, 95% CI 2.63 to 8.62). Childhood circumstances contributed substantially (24%) to the health differences between these educational groups. Nearly two thirds (63%) of this contribution was shared with behavioural factors adopted by early adulthood, and 17% with current circumstances. Health behaviours, smoking especially, were strongly contributed to educational health differences. CONCLUSION: To develop means for avoiding undesirable trajectories along which poor health and health differences develop, it is necessary to understand the pathways to health inequalities and know how to improve the living conditions of families with children. PMID- 19476662 TI - [Health promotion by regional health agencies]. PMID- 19476661 TI - Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility. AB - BACKGROUND: Contamination of the uterine lumen with bacteria is ubiquitous in cattle after parturition. Some animals develop endometritis and have reduced fertility but others have no uterine disease and readily conceive. The present study tested the hypothesis that postpartum cattle that develop persistent endometritis and infertility are unable to limit the inflammatory response to uterine bacterial infection. METHODS: Endometrial biopsies were collected several times during the postpartum period from animals that were subsequently infertile with persistent endometritis (n = 4) or had no clinical disease and conceived to first insemination (n = 4). Quantitative PCR was used to determine the expression of candidate genes in the endometrial biopsies, including the Toll-like receptor (TLR 1 to 10) family of innate immune receptors, inflammatory mediators and their cognate receptors. Selected proteins were examined by immunohistochemistry. RESULTS: The expression of genes encoding pro-inflammatory mediators such as interleukins (IL1A, IL1B and IL6), and nitric oxide synthase 2 (NOS2) were higher during the first week post partum than subsequently. During the first week post partum, there was higher gene expression in infertile than fertile animals of TLR4, the receptor for bacterial lipopolysaccharide, and the pro-inflammatory cytokines IL1A and IL1B, and their receptor IL1R2. The expression of genes encoding other Toll-like receptors, transforming growth factor beta receptor 1 (TGFBR1) or prostaglandin E2 receptors (PTGER2 and PTGER4) did not differ significantly between the animal groups. Gene expression did not differ significantly between infertile and fertile animals after the first week postpartum. However, there were higher ratios of IL1A or IL1B mRNA to the anti inflammatory cytokine IL10, during the first week post partum in the infertile than fertile animals, and the protein products of these genes were mainly localised to the epithelium of the endometrium. CONCLUSION: Cattle may maintain fertility by limiting the inflammatory response to postpartum bacterial infection in the endometrium during the first week after parturition. PMID- 19476663 TI - [Evaluation of general practitioners' involvement in the appropriate and good use of prescription drugs]. AB - Public health policy is committed to support best practice and the good use of prescription drugs. The law passed in August 2004 to reform social health insurance aims to improve the use, consumption and prescription of medication, essentially to fight against the iatrogenic risk due to drug interaction. The study analyses how general practitioners translate this health policy into practice. 528 general practitioners (GPs) in South-Eastern France participated in a telephone-survey. The questionnaire's objective was to assess GPs' involvement in providing information to patients on the risks of self-medication and on the prevention of drug iatrogenicity. Results show that the identification of drug iatrogenicity is well integrated into practice (87,3% of GPs report doing it frequently), although giving information to patients about risks of self medication is less regular (46%). Rural GPs are more involved in identifying iatrogenic risks rather than their urban counterparts. Heavy workloads, and lack of time and coordination between prescribing doctors seem to be factors which emerge as strongly hindering GPs' involvement into this type of prevention. PMID- 19476664 TI - [Factors associated with tuberculosis treatment non-compliance in Antananarivo city, Madagascar]. AB - A retrospective epidemiological study of patients' medical records (n = 442) was conducted in one of the tuberculosis (TB) treatment centers in the city of Antananarivo, to identify risk factors of treatment default. Results show that males give up treatment more than women (OR=1,81 [1,13; 3,03]). Among those living farthest away from the center, patients younger than 30 years old tend to be more irregular in the follow-up of their treatment (OR=3,43 [1,16; 10,15]). There is no statistically significant relationship between TB treatment default and the patient's age, the clinical form, the therapeutic regime or the place of residence. Managers of treatment centers should be more aware and vigilant regarding male and young TB patients presenting these characteristics and should adapt methods and means for follow-up according to these risk factors. PMID- 19476665 TI - [Estimating emergency hospital admissions to gauge short-term effects of air pollution: evaluation of health data quality]. AB - The study of the short-term effects and health impact of air pollution is carrier out by the ERPURS regional surveillance program which utilizes hospitalization data obtained from the French hospital information system (PMSI) to determine these links. This system does not permit the distinction between emergency hospital admissions from scheduled ones, which cannot be related to short term changes in air pollution levels. This study examines how scheduled admissions affect the quality of the health indicators used to estimate air pollution effects. This indicator is compared to three new emergency hospitalisation indicators reconstructed based on data from the public hospitals in Paris, partly from the PMSI data and partly with data from an on-line emergency network that regroups all of the computerized emergency services. According to the pathology, scheduled admissions present a difficulty which affects the capacity to highlight the weakest risks with any precision. PMID- 19476666 TI - [Newborn babies' health in Rwanda: evolution of factors associated with neonatal mortality trends]. AB - In spite of increasing attention for maternal and child health, neonatal mortality (before the age of one month) represents a significant part of infant mortality in sub-Saharan Africa. Several demographic and health surveys show the lack of any major improvement since the 1980s in Rwanda, and despite some indication of minor improvement, any real progress has been countered by periods of aggravation of the situation. However, a noticeable decrease in neonatal mortality seems to have begun since the year 2000. This study describes the evolution of the determinants of neonatal mortality between 1980 and 2000 and the obstacles that hinder its sustainable decline. Regressive logistical analyses conducted with data on several different generations of newborns showed the persistence of some unfavourable factors and conditions, such as the short period of time between births of babies carried to term and premature births. Nevertheless, although the conditions for pregnancy and delivery are still insufficient, the quality of pre-natal and newborn care seems to be improving. PMID- 19476667 TI - [Principles and stakes of external communication of healthcare networks: the case of heathcare networks for health services accessibility]. AB - Healthcare networks which purpose is to manage patients through better coordination of the care, need to develop a communication strategy to be recognized by the public and by healthcare professionals and to be inserted in the healthcare landscape. We firstly will present legal requirements related to external communication of healthcare networks. Then, we will describe the different tools which can be used to communicate about healthcare networks in its area, with the example from a healthcare network for health services accessibility. In the French Public health code, the legal status and the ethical charter of the healthcare network have to be delivered to the healthcare professionals in its area and to the patients. Moreover, the example healthcare network informed collectively and individually the healthcare professionals of its area about its activities. It made it known to the public by the way of departmental prevention manifestations and health education sessions in community social associations. From these examples, we will conduct an ethical reflection on the modalities and stakes of the external communication of healthcare networks. PMID- 19476668 TI - [Community development in Quebec : the contribution of collective intelligence]. AB - This article introduces guidelines and certain applications of a national plan and mechanism currently deployed in several regions of Quebec for advancing knowledge on community development. This scheme relies upon the collective intelligence of communities and supports the efforts of various stakeholders in order to improve population living conditions, health and welfare. It primarily distinguishes itself by granting equal importance to quantitative data collected from administrative files and to qualitative data acquired by acknowledging and processing perceptions and observations which arise from actors working in community development. These data are used to support the preparation and planning of interventions implemented according to the socio-economic and socio health situation of the communities and their potential for development. PMID- 19476669 TI - [The organization and management of health services during mine clearance operations in Finistere]. AB - The regional social affairs and health services department (DDASS) of Finistere in France, in cooperation with first-aid workers, the town hall and the police headquarters, have developed and refined a method for medical evacuations of people during mine clearance in the area of Brest. It consists of conducting a census of the population in their place of residence, identifying the hospitalisation needs, and organising their management and care provided by the first-aid workers. Having been applied and put into practice since 2003, this method is reliant on tools created by the regional social affairs and health services department of. It is frequently used and has proven its effectiveness. PMID- 19476670 TI - [Social disability and public hospitals: towards a model of resource allocation]. AB - A recent study to measure social disability used the results of a questionnaire administered to 696 patients between March 14th and April 7th 2007 which showed that three-quarters of the population surveyed have a social disability. Major determinants of social disadvantage are found using three specific indicators: income, assets and home-interior comfort. A greater deterioration of poor health status was not particularly noted within the most socially disadvantage group of patients, and social disability did not lead to actual over-consumption of medical products or services. People with social disabilities remained hospitalised more than 1.5 days over the average length of hospital stay which accounts for an inferred additional costs to hospital budgets equivalent to 10.3 million ?. The article proposes a model for measuring social disability that can be used routinely upon patient admission to identify socially disadvantaged cases in order to offer those patients specific and tailored assistance and reduce the length of their stay. This model may also support public health policy monitoring. PMID- 19476671 TI - [Maternal and child protection (PMI) and kindergarten: a meeting... to serve the needs of children]. PMID- 19476672 TI - [Do economic actors have a role to play in public health decision - making and defining strategic directions?]. PMID- 19476674 TI - A valid two-item food security questionnaire for screening HIV-1 infected patients in a clinical setting. AB - OBJECTIVE: To validate a two-item food security questionnaire (FSQ) for use in a clinical setting to screen HIV-1 infected patients for food insecurity. DESIGN: The present study was a questionnaire-based survey of forty-nine subjects attending an HIV clinic. Subjects completed a two-item questionnaire and a six item validated FSQ contemporaneously. RESULTS: A strong correlation was found between the two-item and six-item FSQ (rho = 0.895; 95 % CI 0.821, 0.940; P < 0.0001). Cronbach's alpha coefficient was found to be 0.94 and 0.90 for the two item and six-item FSQ, respectively. The two-item FSQ yielded a sensitivity of 100 % (95 % CI 75, 100) and a specificity of 78 % (95 % CI 61, 90). The negative predictive value was found to be 100 % (95 % CI 88, 100). CONCLUSIONS: The results of the present study suggest that the two-item FSQ is a valid, reliable and sensitive screening tool of food insecurity in people living with HIV in a clinical setting. PMID- 19476675 TI - Impact evaluation of the Northern Fruit and Vegetable Pilot Programme - a cluster randomised controlled trial. AB - OBJECTIVE: The purpose of this impact evaluation was to measure the influence of a government of Ontario, Canada health promotion initiative, the Northern Fruit and Vegetable Pilot Programme (NFVPP), on elementary school-aged children's psychosocial variables regarding fruit and vegetables, and fruit and vegetable consumption patterns. DESIGN: A cluster-randomised controlled trial design was used. The NFVPP consisted of three intervention arms: (i) Intervention I: Free Fruit and Vegetable Snack (FFVS) + Enhanced Nutrition Education; (ii) Intervention II: FFVS-alone; and (iii) Control group. Using the Pro-Children Questionnaire, the primary outcome measure was children's fruit and vegetable consumption, and the secondary outcome measures included differences in children's awareness, knowledge, self-efficacy, preference, intention and willingness to increase fruit and vegetable consumption. SETTING/SUBJECTS: Twenty six elementary schools in a defined area of Northern Ontario were eligible to participate in the impact evaluation. A final sample size of 1,277 students in grades five to eight was achieved. RESULTS: Intervention I students consumed more fruit and vegetables at school than their Control counterparts by 0.49 serving/d (P < 0.05). Similarly, Intervention II students consumed more fruit and vegetables at school than Control students by 0.42 serving/d, although this difference was not statistically significant. Among students in both intervention groups, preferences for certain fruit and vegetables shifted from 'never tried it' towards 'like it'. CONCLUSIONS: The NFVPP resulted in positive changes in elementary school-aged children's fruit and vegetable consumption at school, and favourable preference changes for certain fruit and vegetables. PMID- 19476676 TI - A new FFQ designed to measure the intake of fatty acids and antioxidants in children. AB - OBJECTIVE: The present paper describes the systematic development of an FFQ to assess the intake of fatty acids and antioxidants in school-aged children. In addition, a validation study applying 24 h dietary recalls was performed. DESIGN: Using the variance-based Max_r method, a list of eighty-two foods was compiled from data obtained by 3 d weighed dietary records. The foods were used to design an FFQ, the comprehensibility of which was evaluated in a feasibility study. In addition, the FFQ was validated in a subset of 101 children from the German Infant Nutritional Intervention Study (GINI PLUS) against one 24 h dietary recall. RESULTS: The feasibility study attested a good acceptance of the FFQ. Mean intake of foods compared well between the FFQ and the 24 h dietary recall, although intake data generated from the FFQ tended to be higher. This difference became less apparent at the nutrient level, although the estimated average consumption of arachidonic acid and EPA using the FFQ still exceeded values recorded with the 24 h recall method by 45 % and 29 %, respectively. CONCLUSIONS: On the basis of the systematic selection process of the food list, the established practicability of the FFQ and the overall plausibility of the results, the use of this FFQ is justified in future epidemiological studies. PMID- 19476677 TI - Reliability and validity of a semi-quantitative FFQ for sodium intake in low income and low-literacy Brazilian hypertensive subjects. AB - OBJECTIVE: To assess the reliability and validity of an FFQ to evaluate dietary patterns of Na consumption among low-income and low-literacy Brazilian hypertensive subjects. DESIGN: The initial FFQ was submitted to content analysis with the pre-test administered to fifteen subjects. Reliability was evaluated according to the reproducibility criterion, with interviewer administration of the FFQ twice within a 15 d interval. Validity was assessed against a 24 h recall (132 subjects), a 3 d diet record (121 subjects) and a biomarker (24 h urinary Na; 121 subjects). To test the correlation with the biomarker, discretionary salt was added to the FFQ Na values. SETTING: A large urban teaching hospital in south eastern Brazil. SUBJECTS: The study was based on 132 randomly selected subjects (eighty-three women and forty-nine men) aged 18 to 85 years. RESULTS: Kappa coefficients ranged from 0.79 to 0.98, confirming the reproducibility of the FFQ. There was no correlation between urinary Na excretion, the FFQ and the 24 h recall for the general sample, although significant correlations had been observed when methods were summed up (24 h recall + discretionary salt + FFQ; 0.32, P = 0.01). The addition of discretionary salt significantly improved the biomarker-based FFQ validity, with correlation coefficients varying from 0.19 (general sample) to 0.31 (female sub-sample). CONCLUSIONS: The developed FFQ demonstrated satisfactory evidence of validity and reliability and can be used as an important complementary tool for the evaluation of Na intake among Brazilian hypertensive subjects. PMID- 19476678 TI - Sweets and sugar-sweetened soft drink intake in childhood in relation to adult BMI and overweight. The Cardiovascular Risk in Young Finns Study. AB - OBJECTIVE: To investigate the associations of BMI and overweight in adulthood with consumption of sweets and sugar-sweetened soft drinks in childhood and with the change in consumption between childhood and adulthood. DESIGN: Longitudinal 21-year follow-up study of Finnish children and adolescents from childhood to adulthood. SETTING: The Cardiovascular Risk in Young Finns Study, comprising participants from both eastern and western Finland. SUBJECTS: Boys (n 967) and girls (n 1172) aged 3-18 years at baseline in 1980. RESULTS: The increase in consumption of sugar-sweetened soft drinks from childhood to adulthood was directly associated with BMI in adulthood in women (b = 0.45, P = 0.0001) but not in men. In women, BMI increased by 0.45 kg/m2 for every 10-unit increase per month. Consumption of sweets and sugar-sweetened soft drinks in childhood and adolescence was not associated with BMI in adulthood. The change in consumption of sweets was not associated with BMI in adulthood. The increase in the consumption of sugar-sweetened soft drinks from childhood to adulthood was associated with being overweight (OR = 1.90, 95 % CI 1.38, 2.61) in women, but not in men. No association was found between overweight (BMI >or= 25 kg/m2) in adulthood and consumption of sweets in childhood or the change in consumption from childhood to adulthood. CONCLUSIONS: We conclude that direct associations exist between adulthood overweight and BMI and an increase in consumption of sugar-sweetened soft drinks in women. Thus sugar-sweetened soft drinks consumption may be important when considering weight management in women. PMID- 19476679 TI - Unexpectedly high early prevalence of anaemia in 6-month-old breast-fed infants in rural Bangladesh. AB - OBJECTIVE: To determine the prevalence of anaemia and maternal and infant factors associated with Hb values in infants at 6 months of age in rural Bangladesh. DESIGN: Infants (born to mothers supplemented with Fe-folic acid from mid pregnancy) were visited at birth and 6 months of age. Mothers' anthropometric status, and infants' birth weight, gestational age at birth, weight and Hb concentration at 6 months were measured. Household socio-economic and demographic data, infant feeding practices and health status were collected using a pre tested structured questionnaire. SETTING: Rural Bangladesh. SUBJECTS: Four hundred and two infants. RESULTS: For the total cohort (n 402), the range of anaemia prevalence values was from 30.6 % using a cut-off value of Hb < 95 g/l to 71.9 % using a value of Hb < 110 g/l. Birth weight and month of birth were the only factors positively associated with infant Hb in a linear regression model (P = 0.008 and 0.011, respectively). CONCLUSIONS: There was an unexpectedly high prevalence of anaemia in infants at 6 months of age, before the assumed period of vulnerability. Hb at this age tended to be higher in those with higher birth weight. We also found a season effect on Hb, as it tended to be higher as the study progressed. The high prevalence of anaemia at such an early age needs to be addressed to minimize the disease's long-term consequences. PMID- 19476680 TI - Acceptability and use of iron and iron-alloy cooking pots: implications for anaemia control programmes. AB - OBJECTIVE: To evaluate the acceptability of iron and iron-alloy cooking pots prior to an intervention trial and to investigate factors affecting retention and use. DESIGN: Pre-trial research was conducted on five types of iron and iron alloy pots using focus group discussions and a laboratory evaluation of Fe transfer during cooking was undertaken. Usage and retention during the subsequent intervention trial were investigated using focus group discussions and market monitoring. SETTING: Three refugee camps in western Tanzania. SUBJECTS: Refugee health workers were selected for pre-trial research. Mothers of children aged 6 59 months participated in the investigation of retention and use. RESULTS: Pre trial research indicated that the stainless steel pot would be the only acceptable type for use in this population due to excessive rusting and/or the high weight of other types. Cooking three typical refugee dishes in stainless steel pots led to an increase in Fe content of 3.2 to 17.1 mg/100 g food (P < 0.001). During the trial, the acceptability of the stainless steel pots was lower than expected owing to difficulties with using, cleaning and their utility for other purposes. Households also continued to use their pre-existing pots, and stainless steel pots were sold to increase household income. CONCLUSIONS: Pre trial research led to the selection of a stainless steel pot that met basic acceptability criteria. The relatively low usage reported during the trial highlights the limitations of using high-value iron-alloy cooking pots as an intervention in populations where poverty and the availability of other pots may lead to selling. PMID- 19476681 TI - Replication and heterogeneity in gene x environment interaction studies. PMID- 19476682 TI - Time to agree guidelines and apply an ethical framework for public health nutrition. PMID- 19476684 TI - What is the food and drink industry doing in nutrition conferences? PMID- 19476686 TI - PepsiCo marketing policy. PMID- 19476687 TI - Marketing of unhealthy food to young children. Brazilian David and multinational Goliath. PMID- 19476688 TI - Cognitive behavioural therapy for major psychiatric disorder: does it really work? A meta-analytical review of well-controlled trials. AB - BACKGROUND: Although cognitive behavioural therapy (CBT) is claimed to be effective in schizophrenia, major depression and bipolar disorder, there have been negative findings in well-conducted studies and meta-analyses have not fully considered the potential influence of blindness or the use of control interventions. METHOD: We pooled data from published trials of CBT in schizophrenia, major depression and bipolar disorder that used controls for non specific effects of intervention. Trials of effectiveness against relapse were also pooled, including those that compared CBT to treatment as usual (TAU). Blinding was examined as a moderating factor. RESULTS: CBT was not effective in reducing symptoms in schizophrenia or in preventing relapse. CBT was effective in reducing symptoms in major depression, although the effect size was small, and in reducing relapse. CBT was ineffective in reducing relapse in bipolar disorder. CONCLUSIONS: CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates. It is effective in major depression but the size of the effect is small in treatment studies. On present evidence CBT is not an effective treatment strategy for prevention of relapse in bipolar disorder. PMID- 19476689 TI - The links between prenatal stress and offspring development and psychopathology: disentangling environmental and inherited influences. AB - BACKGROUND: Exposure to prenatal stress is associated with later adverse health and adjustment outcomes. This is generally presumed to arise through early environmentally mediated programming effects on the foetus. However, associations could arise through factors that influence mothers' characteristics and behaviour during pregnancy which are inherited by offspring. METHOD: A 'prenatal cross fostering' design where pregnant mothers are related or unrelated to their child as a result of in vitro fertilization (IVF) was used to disentangle maternally inherited and environmental influences. If links between prenatal stress and offspring outcome are environmental, association should be observed in unrelated as well as related mother-child pairs. Offspring birth weight and gestational age as well as mental health were the outcomes assessed. RESULTS: Associations between prenatal stress and offspring birth weight, gestational age and antisocial behaviour were seen in both related and unrelated mother-offspring pairs, consistent with there being environmental links. The association between prenatal stress and offspring anxiety in related and unrelated groups appeared to be due to current maternal anxiety/depression rather than prenatal stress. In contrast, the link between prenatal stress and offspring attention deficit hyperactivity disorder was only present in related mother-offspring pairs and therefore was attributable to inherited factors. CONCLUSIONS: Genetically informative designs can be helpful in testing whether inherited factors contribute to the association between environmental risk factors and health outcomes. These results suggest that associations between prenatal stress and offspring outcomes could arise from inherited factors and post-natal environmental factors in addition to causal prenatal risk effects. PMID- 19476690 TI - Response to 'The social determinants of psychosis in migrant and ethnic minority populations: a public health tragedy'. PMID- 19476691 TI - The effects of antipsychotics on brain structure: what have we learnt from structural imaging of schizophrenia? PMID- 19476692 TI - The influence over a period of 8 years of patterns of prescribing palivizumab for patients with and without congenitally malformed hearts, and in admissions to paediatric intensive care. AB - OBJECTIVES: To describe the pattern of prescribing for palivizumab in the Glasgow area over the period 1999 through 2007, and to compare recent prescribing to the current recommendations by the Joint Committee on Vaccination and Immunisation of the United Kingdom Department of Health. Our secondary objective was to describe admissions to paediatric intensive care in patients with respiratory syncytial virus receiving palivizumab. SETTING: Tertiary children's hospital out-patient immunisation clinic and paediatric intensive care unit. DESIGN: Prospective analysis of prescribing and admissions data for the period 1999 through 2007. OUTCOME MEASURES: Number of prescriptions and admissions to the paediatric intensive care unit. RESULTS: The number of children receiving palivizumab annually initially rose more than 5-fold, from 17 in the season of 1999 and 2000 versus 115 in 2004 and 2005, although it has declined in the past 2 years, to 63 in 2006 and 2007, following publication of the recommendations of the Joint Committee on Vaccination and Immunisation established by the United Kingdom Department of Health. There has been no significant change in demographics of patients during this period. Prior to publication of these recommendations, 35 of 44 (80%) patients with congenitally malformed hearts who received palivizumab in the season of 2005 and 2006 deviated from the current recommendations, compared to 5 of 51 (10%) who received palivizumab for non-cardiac indications. No patients who received palivizumab required admission to the paediatric intensive care unit with proven respiratory syncytial virus infection over the 8 year period. CONCLUSIONS: The number of children receiving palivizumab initially increased significantly, although it has now fallen following implementation of national recommendations. Much prescribing, particularly for children with congenitally malformed hearts, did not fulfil current recommendations. The absence of admissions to paediatric intensive care reflects the success of targeted immunisation in our population. PMID- 19476693 TI - Pulmonary hypertension associated with congenital cardiac disease. PMID- 19476694 TI - Aortic aneurysms and dissection diagnosed by computed tomography 19 years after repair of coarctation. PMID- 19476695 TI - Effects of amino acid neurotransmitters on spontaneous muscular activity of the rumen amphistome, Gastrothylax crumenifer. AB - Amino acid neurotransmitters play an important role in regulating neuromuscular activity of helminth parasites. The present study aimed to investigate the effects of different amino acid neurotransmitters [L-glutamate, glycine, gamma aminobutyric acid (GABA)] on spontaneous muscular activity of isometrically mounted Gastrothylax crumenifer. L-Glutamate caused a significant increase in the amplitude and frequency of spontaneous contractions of rumen fluke at 10(-7)-10( 4) m and at 10(-5)-10(-4) m concentrations, respectively. Glycine application (10(-7)-10(-3) m) produced a significant decrease in the amplitude and frequency of spontaneous muscular contractions in a concentration-dependent manner, as compared to control amplitude (0.53 +/- 0.02 g) and frequency (51 +/- 4.65/5 min). Similarly, GABA produced a significant (P < 0.05) decrease in amplitude, baseline tension and frequency of spontaneous muscular contractions of G. crumenifer. To further substantiate the GABA effect, GABAA receptor antagonists, picrotoxin and bicuculline were applied. Picrotoxin (10(-5)-10(-3) m) caused a significant (P < 0.05) increase in amplitude, baseline tension and frequency of the rumen fluke as compared to control; whereas bicuculline did not elicit any observable effect in these attributes in isometrically mounted rumen flukes. These observations suggested that L-glutamate has an excitatory, whereas GABA and glycine have an inhibitory, effect on the spontaneous muscular activity of G. crumenifer. PMID- 19476696 TI - Separation and purification of rutin and acaciin from the chinese medicinal herb Herba Cirsii by combination of macroporous absorption resin and high-speed counter-current chromatography. AB - A preparative high-speed counter-current chromatography (HSCCC) method for isolation and purification of rutin and acaciin from the Chinese medicinal herb Herba Cirsii was successfully established. The crude extracts obtained from Herba Cirsii by water under reflux were subjected to a macroporous resin column and eluted with 10% and 60% ethanol, respectively. The fraction of 60% ethanol was used as the sample for HSCCC separation of rutin and acaciin. The two-phase solvent system used for the separation was ethyl acetate-n-butanol-water (5:1.5:5, v/v) and the upper phase was used as the stationary phase. Rutin (25.2 mg) and acaciin (21.8 mg) with a purity of 99.2% and 99.6%, respectively, were purified successfully from 60 mg of sample. The chemical structures of rutin and acaciin were identified by 1H-NMR and 13C-NMR. PMID- 19476697 TI - Preparative purification of morroniside and loganin from Fructus corni by combination of macroporous absorption resin and HSCCC. AB - A method for preparative purification of loganin and morroniside from Fructus corni was established by combination of macroporous absorption resin column separation and high-speed counter-current chromatography (HSCCC). The crude extracts obtained from Fructus corni by ultrasonic extraction with 50% methanol were subjected to separation on a macroporous resin column and then eluted with 15% and 40% ethanol, respectively. A fraction of 40% ethanol was used as the sample for separation of morroniside and loganin by HSCCC. The two-phase solvent system used for HSCCC separation was n-butanol-methanol-1% acetic acid water (4:1:6, v/v). The upper phase was used as the stationary phase of HSCCC. Morroniside (28.7 mg) of 97.8% purity and loganin (11.5 mg) of 98.6% purity were obtained in a one-step HSCCC separation from 50 mg of sample. The structures of morroniside and loganin were identified by 1H-NMR and 13C-NMR. PMID- 19476698 TI - Separation and purification of epimedin A, B, C, and icariin from the medicinal herb Epimedium brevicornum maxim by dual-mode HSCCC. AB - Epimedium brevicornum Maxim is a famous medicinal herb which has been widely used for the treatment of impotence, infertility, osteoporosis, cardiovascular diseases, amnesia, and senile functional diseases. A dual-mode high-speed counter current chromatographic method is developed for the separation and purification of four bioactive flavonoids from the medicinal herb Epimedium brevicornum Maxim. The crude flavonoids are obtained by extraction with ethyl acetate and ethanol from the dried aerial parts of Epimedium brevicornum Maxim under sonication. High speed counter-current chromatography with a two-phase solvent system composed of n-butanol-ethyl acetate-water (3:7:10, v/v) is performed using a dual-mode method, which yields 3.2 mg of epimedin A at a purity of 98.2%, 5.5 mg of epimedin B at a purity of 92.6%, 12.7 mg of epimedin C at a purity of 90.4%, and 42.9 mg of icariin at a purity of 96.8% based on the HPLC analysis. The recoveries are 95.2%, 89.4%, 91.1%, and 94.8%, respectively. The isolation of these flavonoids in adequate amounts makes them readily available for structure activity relationship studies and for quality control of the herbal medicine. PMID- 19476699 TI - Purification of rutin and nicotiflorin from the flowers of Edgeworthia chrysantha Lindl. by high-speed counter-current chromatography. AB - An ethanol extract of air-dried flowers of Edgeworthia chrysantha Lindl. was partitioned between water and petroleum, ethyl acetate, and n-butanol. The n butanol extraction was initially purified by silica gel column chromatography to give a partially purified sample. The bioactive compound rutin, along with nicotiflorin, were successfully separated from the partially purified sample by high-speed counter-current chromatography. The two compounds were isolated from the plant of Edgeworthia genus for the first time. The two-phase solvent system used was composed of ethyl acetate-n-butanol-water at an optimized ratio of 4:1:5 (v/v/v). High-speed counter-current chromatography yielded, from 108 mg of the partially purified extract, 53 mg rutin and 32 mg nicotiflorin with 92.5% and 92.2% recovery, with each at over 96.5% purity by high-performance liquid chromatography analysis. Their structures were identified by 1H NMR and 13C NMR. PMID- 19476700 TI - Separation of five isomers of dihydroxybenzoic acid by high-speed counter-current chromatography with dual-rotation elution method. AB - Five small molecular isomers, 2,3-, 2,4-, 2,6-, 3,4-, and 3,5-dihydroxybenzoic acid, were successfully separated in one step with solvent system n-hexane-ethyl acetate-methanol-water (1:5:1.5:5) on high-speed counter-current chromatography (HSCCC). A new method, dual-rotation elution, was successfully used to decrease separation time and increase resolution. Five peak factions were eluted within 850 min. HSCCC became an efficient method to separate small molecular isomers from intermediates and products of organic synthesis, especially with the dual rotation elution method. PMID- 19476701 TI - A high-speed counter-current chromatography- HPLC-DAD method for preparative isolation and purification of two polymethoxylated flavones from Taraxacum mongolicum. AB - After an initial clean-up step on silica gel, a preparative high-speed counter current chromatography coupled with on-line high-performance liquid chromatography-diode array detection method (HSCCC-HPLC-DAD) was successfully developed for the isolation and determination two polymethoxylated flavones, 3',4',7-trimethoxyquercetin and artemetin, from the aerial part of Taraxacum mongolicum. The HSCCC separation was performed with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (6:5:6:5, v/v/v/v) at a flow rate of 1.5 mL/min and at 800 rpm. The on-line purity monitoring of a representative aliquot from each HSCCC fraction was operated automatically. Using this method, fractions with high purity were collected. The HSCCC purification step was done in 5 h, and afforded 84.2 mg of 3',4',7-trimethoxyquercetin and 52.3 mg of artemetin, with purity over 98% from 200 mg of the enriched extracts of T. mongolicum. The structures were identified by electorspray ionization mass spectrometry and 1H NMR experiments. To our best knowledge, 3',4',7 trimethoxyquercetin was obtained from the plant of genus Taraxacum for the first time by our group. This hyphenated method could be used for the preparation of bioactive compounds with higher purity from natural products. PMID- 19476702 TI - Separation of cyclosporins and other antibiotics by HSCCC. AB - Applications of high-speed counter-current chromatography (HSCCC) for the separations of antibiotics, cyclosporins and isoflavones, by a marine Micromonospora and macrolides including tacrolimus, ascomycin, and dihydroFk-506 are described. The application of silver ion HSCCC technique in the separation of tacrolimus from its components is also described. PMID- 19476704 TI - Effect of mobile phase pH and organic content on LC-MS analysis of nucleoside and nucleotide HIV reverse transcriptase inhibitors. AB - The HIV-1 reverse transcriptase inhibitors tenofovir (TFV), emtricitabine (FTC), and lamivudine (3TC) are widely used in the treatment of HIV-1-infected persons and are now being considered as chemoprophylactic drugs for the prevention of sexual HIV transmission. Assays that measure these drugs after either oral or topical application are critical to the understanding of the pharmacokinetic profiles of the drugs and allow a rational design of chemoprophylaxis modalities for evaluation in macaque models and human trials. We developed a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) method for sensitive measurement of FTC, 3TC, and TFV in plasma from macaques. To achieve detection limits of 10 pg on column, the plasma analytes were measured using acidic mobile phase and positive electrospray ionization MS-MS detection. However, this caused various chromatographic peak distortions, which were minimized by using mobile phase additives that induced ion-pairing interactions. Chromatographic peak tailing was minimized by adjusting the organic mobile phase concentration while considering the simultaneous effect of organic content on buffer and analyte pKa. Injection solution interferences were corrected by chromatographic peak focusing using column switching. The final method provides simultaneous measurement of all three analytes with a wide linear range of 1-3000 ng/mL using 0.1 mL plasma (10 pg on column) and coefficients of variation from 5% to 15% in the high ng/mL concentration range and from 16% to 20% in the low ng/mL concentration range. PMID- 19476705 TI - New method for stock-tank oil compositional analysis. AB - A new method for accurately determining stock-tank oil composition to normal pentatriacontane using gas chromatography is developed and validated. The new method addresses the potential errors associated with the traditional equipment and technique employed for extended hydrocarbon gas chromatography outside a controlled laboratory environment, such as on an offshore oil platform. In particular, the experimental measurement of stock-tank oil molecular weight with the freezing point depression technique and the use of an internal standard to find the unrecovered sample fraction are replaced with correlations for estimating these properties. The use of correlations reduces the number of necessary experimental steps in completing the required sample preparation and analysis, resulting in reduced uncertainty in the analysis. PMID- 19476703 TI - GC-MS evaluation of a series of acylated derivatives of 3,4 methylenedioxymethamphetamine. AB - A series of acylated derivatives of 3,4-methylenedioxy-methamphetamine (3,4-MDMA) are prepared and evaluated in gas chromatography-mass spectrometry (GC-MS) studies. The perfluoroalkyl amides of 3,4-MDMA show the lowest GC retention, while the aromatic amides such as the benzamide show the greatest retention on the dimethylpolysiloxane stationary phase (Rtx-1). The mass spectral properties of the acetyl, propionyl, and butyryl derivatives all show a base peak at m/z 58 which is the base peak for the underivatized 3,4-MDMA. All acylated derivatives provide mass spectral information (m/z 162) to identify the three-carbon side chain for 3,4-MDMA. The perfluoroalkyl amides yield several unique mass spectral fragments for specific identification of 3,4-MDMA. MS fragmentation pathways are illustrated and validated using analogous deuterated derivatives. A combination of excellent chromatographic properties and unique mass spectral fragments allows the perfluoroalkyl amides to provide maximum specific structural information in the GC-MS analysis of 3,4-MDMA. PMID- 19476706 TI - Development and validation of a stability-indicating RP-HPLC method for assay of alphamethylepoxide and estimation of its related compounds. AB - Alphamethylepoxide (16alpha-methyl-Delta1,4-pregnadiene-9beta-11beta-oxide 17alpha,21-diol-3,20-dione) is a key intermediate for the synthesis of various active pharmaceutical ingredients of steroid compounds. A stability-indicating reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the assay of alphamethylepoxide and estimation of its related compounds has been developed and validated. It can accurately quantitate alphamethylepoxide in the presence of numerous structurally related compounds (including the beta-epimer, known as betamethylepoxide). This method can also adequately separate most of the impurities from each other and estimate their quantities in alphamethylepoxide samples. The stability-indicating capability of this method has been demonstrated by adequate separation of the degradation products from alphamethylepoxide in stress degraded and aged stability samples. A 15 cmx4.6 mm i.d. ACE C18 HPLC column is the primary column used in this method, and a 15 cmx4.6 mm i.d. A Develosil ODS UG column serves as the alternative column. The mobile phase consisted of 10 mM sodium sulfate, 0.05% (v/v) phosphoric acid, and acetonitrile. This method can accurately assay the content of alphamethylepoxide (in a given lot) with a % relative standard deviation of less than one. It can also estimate individual impurities down to 0.05% level compared with the alphamethylepoxide peak in the sample. PMID- 19476707 TI - Development of an analytical methodology for simultaneous determination of vincristine and doxorubicin in pharmaceutical preparations for oncology by HPLC UV. AB - A high-performance liquid chromatography-UV methodology (lambda=230 nm) was developed and validated for the simultaneous determination of vincristine and doxorubicin in pharmaceutical preparations used in oncology. The chromatography was carried out on a C18 column using acetonitrile 90% in water-potassium hydrogenphosphate buffer 50 mM, pH 3.2+/-0.1 (32:68, v/v) as mobile phase at a flow rate of 1.5 mL/min. The method proved to be specific, exact, and accurate, in accordance with the ICH standards, presenting linearity in the 1-5 microg/mL and 5-100 microg/mL intervals, and detection (0.19x0.51 microg/mL) and quantification (0.63x1.7 microg/mL) limits for vincristine and doxorubicin, respectively. PMID- 19476708 TI - Effects of ionic liquid on the separation of 2-chlorophenol and 2,4,6 trichlorophenol in RP-HPLC. AB - In this study, the use of ionic liquids as additives in the separation of 2 chlorophenol and 2,4,6-trichlorophenol in reversed-phase high-performance liquid chromatography is reported. The ionic liquids used were 1-butyl-3 methylimidazolium tetrafluoroborate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-ethyl-3-methylimidazolium methylsulfate ([EMIm][MS]), and 1 octyl-3-methylimidazolium methylsulfate ([OMIm][MS]), because of their high hydrophobicity and good solvating properties. The effects of the ionic liquid on retention factor and resolution, and the change of detector response using the different ionic liquids were studied. Separation with the [MS] anion ionic liquid in the eluent resulted in better resolution than with the [BF4] anion ionic liquid. The best result was achieved using 3.0 mM/L of [OMIm][MS] and 1.0 mM/L [EMIm][MS] as mobile phase additives. PMID- 19476709 TI - Quantitative structure-retention relationship models for the prediction of the reversed-phase HPLC gradient retention based on the heuristic method and support vector machine. AB - The heuristic method (HM) and support vector machine (SVM) were used to construct quantitative structure-retention relationship models by a series of compounds to predict the gradient retention times of reversed-phase high-performance liquid chromatography (HPLC) in three different columns. The aims of this investigation were to predict the retention times of multifarious compounds, to find the main properties of the three columns, and to indicate the theory of separation procedures. In our method, we correlated the retention times of many diverse structural analytes in three columns (Symmetry C18, Chromolith, and SG-MIX) with their representative molecular descriptors, calculated from the molecular structures alone. HM was used to select the most important molecular descriptors and build linear regression models. Furthermore, non-linear regression models were built using the SVM method; the performance of the SVM models were better than that of the HM models, and the prediction results were in good agreement with the experimental values. This paper could give some insights into the factors that were likely to govern the gradient retention process of the three investigated HPLC columns, which could theoretically supervise the practical experiment. PMID- 19476712 TI - Effects of fenbendazole on the murine humoral immune system. AB - Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered. PMID- 19476713 TI - Revisiting influences on tumor development focusing on laboratory housing. AB - Spontaneous tumors are reported to occur in 45% to 71% of Sprague-Dawley rats, yet few studies have considered the effect of the sedentary condition of standard laboratory cages on tumorigenesis. Tumor profiles and tumor promoting hormone prolactin were compared in female Sprague-Dawley rats (108) that were allocated into 3 groups: those housed without outside activity (SED group), with twice weekly 1-h sessions of physical activity in large box (PA group), and with regular voluntary running-wheel exercise (EX). Compared with the EX group, SED rats had more and larger tumors throughout most of their lifespan; tumor profiles of PA rats were similar to those of the SED group. A larger percentage of animals in the SED group had tumors (54%), compared with EX rats (38%). At 64 wk, tumors in SED animals included thyroid carcinoma, malignancy, mammary fibroadenoma, cystadenoma, and granuloma, whereas benign mammary gland cysts were most common in EX. Prolactin levels were highest in SED animals at 24 and 52 wk. In conclusion, increased tumor number, increased tumor size, type of spontaneous tumor, and increased prolactin in rats were associated with standard laboratory housing, which limited physical activity, and were not primarily due to aging. PMID- 19476714 TI - A PCR-based strategy for detection of mouse parvovirus. AB - Mouse parvovirus (MPV) infection is difficult to address because it is asymptomatic, persists for as long as 9 wk, and occurs in small subpopulations of mice. The efficacy of a PCR-based cage swabbing strategy for MPV detection was tested. On postinoculation days (PID) 3 through 63, feces were collected from MPV infected SW mice or the wire bars and cage wall above and below the bedding were swabbed. MPV DNA was detected in all cages in all locations on PID 7 and 14 but only below the bedding on PID 21. Swabbing below the bedding detected MPV in most cages through PID 42. Sentinels exposed to soiled cages on PID 7 and 14 but not on PID 21 seroconverted. MPV was detected in feces from all cages until PID 33 and in at least 1 cage until PID 56. In BALB/c mice, MPV was detected in feces and on cage swabs on PID 5 to 14, and 80% of sentinels exposed to soiled cages on PID 7 and 14 seroconverted. In comparison, MPV infection of C57BL/6 mice was detected in feces on PID 5 to 14 and on swabs on PID 5 and 7, and 30% of sentinels exposed to soiled cages on PID 7 and 14 seroconverted. Swabbing of multiple cages in rows in which only 1 cage contained MPV-infected mice was ineffective. In conclusion, swabbing of individual cages can be used in a genotype-dependent manner as an adjunct to soiled bedding sentinels during the first 2 wk of infection. PMID- 19476715 TI - Refinement of telemetry for measuring blood pressure in conscious rats. AB - Although considered the 'gold standard' for measuring blood pressure in laboratory animals, telemetry would benefit from refinement. In the present study, we tested the hypothesis that the small telemetric device used for blood pressure recording in mice would work for rats as well and would serve as an alternative for those studies where abdominal cavity space is quite limited (such as in young animals and pregnant females). Here we report that the use of a smaller and lighter telemetric device implanted in the abdominal aorta of rats led to acquisition of stable and high-quality blood pressure and heart rate data, similar to those obtained by using a larger telemetric device developed for rats. The use of smaller transmitters represents an alternative telemetry technique, especially for those cases in which space in the abdominal cavity is particularly limited such as during pregnancy. PMID- 19476716 TI - Changes in blood parameters and coagulation-related gene expression in pregnant rats. AB - The present study examined changes in maternal blood parameters, particularly those related to blood coagulation, as well as alterations in blood coagulation related gene expression in the liver during gestation in rats. Fibrinogen concentration and platelet count increased as pregnancy progressed whereas prothrombin time and overall activity of vitamin-K-dependent coagulation factors decreased before delivery, suggesting a physiologic response to prevent prolonged bleeding at parturition. Conversely, compared with values for nonpregnant rats, activated partial thromboplastin time was prolonged before delivery and antithrombin time was significantly higher during fetal organogenesis and thereafter, indicating a mechanism to prevent the development of deep tissue thrombosis in dams. DNA microarray analysis revealed no differences in coagulation-related gene expression in the liver on gestation day 13 between pregnant and nonpregnant rats, whereas the gene expression of various fibrinogen related factors, coagulation factors II and X, and the anticoagulation factor related factor leuserpin 2 were increased on gestational day 19. In addition, changes similar to those reported previously in pregnant rats were confirmed. The data obtained from the present study can be used as background data for effective evaluation of reproductive toxicology in rats, and they suggest that the rat is a useful animal model for investigating the mechanisms of disorders in the blood coagulation system that can occur during late pregnancy in women. PMID- 19476717 TI - Comparison of side effects between buprenorphine and meloxicam used postoperatively in Dutch belted rabbits (Oryctolagus cuniculus). AB - One of the challenges facing veterinarians and investigators who use rabbits (Oryctolagus cuniculus) as a surgical model in biomedical research is choosing an appropriate and efficacious postoperative analgesic without systemic complications and side effects. The objective of this study was to evaluate the gastrointestinal side effects associated with the postoperative use of buprenorphine in Dutch Belted rabbits. We also evaluated the analgesic meloxicam as an alternative to opioid administration during the postoperative period. Rabbits were assigned to 1 of 3 treatment groups during the postoperative period after routine ovariohysterectomy: buprenorphine (n = 10), meloxicam (n = 10), and incisional infiltration with bupivicaine (no treatment control; n = 10). Feed intake, fecal production, weight loss, urine output, and other physiologic parameters were monitored and behavior and pain assessments were performed for 7 d after surgery and compared with baseline values collected before surgery. All rabbits showed decreased pellet consumption, fecal production, and weight on day 1 after surgery. This effect was severe in some rabbits that received bupivicaine; therefore treatment of this entire group with metoclopramide, fluids, and hay was instituted to reverse gut stasis. No significant difference in feed consumption and fecal production was present between the buprenorphine- and meloxicam-treated groups. On the basis of these results, meloxicam appears to be a suitable alternative or adjunct to buprenorphine for alleviating postoperative pain with minimal risk of anorexia and gastrointestinal ileus. PMID- 19476718 TI - The effects of age and sex on interest toward movies of conspecifics in Japanese macaques (Macaca fuscata). AB - Previous studies have suggested that images of conspecifics are useful for environmental enrichment for nonhuman primates, but whether the age and sex of the animals alter the effectiveness of such images is unclear. We investigated preferences to movies in Japanese macaques (Macaca fuscata; male and female; age, 2 to 19 y). Each monkey was housed individually in a cage outfitted with a touch sensitive computer display. A subject monkey that touched the display was shown 1 of 30 movies that were recorded at an open enclosure containing their conspecifics. During the experimental sessions, 25 of 38 subjects touched the display at least once. The response duration was longer when monkeys appeared in the movies. The response duration decreased with age in male monkeys but not female monkeys. The results suggested the movies of conspecifics are useful for environmental enrichment, but further consideration seems appropriate for various subpopulations, particularly aged monkeys. PMID- 19476719 TI - Use of food wafers for multiple daily oral treatments in young rats. AB - Many laboratory studies require oral administration of drugs. Dietary administration in food or water is useful, but is not always the best method. Orogastric gavage can be stressful. Here, we describe in detail a relatively stress-free technique that can be applied to multiple daily administrations using a palatable food item. This method was successfully used to administer water or methylphenidate 3 times daily to young pair-housed adolescent rats. PMID- 19476720 TI - Urethral obstruction by seminal coagulum is associated with medetomidine-ketamine anesthesia in male mice on C57BL/6J and mixed genetic backgrounds. AB - Male and female mice were anesthetized by intraperitoneal injection with a mixture delivering 0.5 mg/kg medetomidine and 50 mg/kg ketamine to achieve immobilization for whole-body radiographs and bone densitometry, as part of a phenotypic screen for bone and mineral disorders in mice carrying genetic modifications induced through mutagenesis with N'-ethyl-N'-nitrosourea. Morbidity and mortality occurred in 19 of 628 (3%) of male mice 24 to 72 h after a seemingly uneventful recovery from anesthesia. No morbidity or mortality occurred in 1564 female mice that were similar in age to the affected male mice and that underwent the same procedure. Of the 7 male mice that underwent postmortem examinations, 5 had urinary bladders grossly distended with urine and 1 had ascites. In addition, the pelvic or penile urethra in 5 of the examined male mice was obstructed with seminal coagulum associated with varying degrees of erosion of the urothelial lining and inflammation of the urethra. In 2 of these animals, from which plasma samples were recovered, azotemia, hyperphosphatemia, and hyperkalemia were present. The predilection for delayed morbidity and mortality in males after anesthesia suggests that anesthesia with 0.5 mg/kg medetomidine and 50 mg/kg ketamine is a potential risk factor for obstructive uropathy due to release of seminal coagulum. This adverse effect did not recur when we altered our anesthesia protocol to 10 mg/kg xylazine and 100 mg/kg ketamine. PMID- 19476721 TI - The 'mill-wheel' murmur and computed tomography of intracardiac air emboli. AB - The 'water-wheel' or 'mill-wheel' murmur is classically associated with large intracardiac air emboli and described as a "characteristic splashing auscultatory sound due to the presence of gas in the cardiac chambers." We used 64-slice computed tomography (slice thickness, 0.5 mm; revolution time, 400 msec) and 3D fly-through software imagery to capture previously unreported intracardiac air blood interface dynamics associated with this murmur and ineffective right ventricular contraction in a porcine model. PMID- 19476722 TI - Multisystemic eosinophilia resembling hypereosinophilic syndrome in a colony-bred owl monkey (Aotus vociferans). AB - In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naive, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. PMID- 19476723 TI - Tacrolimus ointment: a novel and effective topical treatment of localized atopic dermatitis in a rhesus macaque (Macaca mulatta). AB - An adult, male, rhesus macaque presented with pruritus and a focal, exudative, inflamed, erythematous skin lesion of approximately 2 cm in diameter on the ventral aspect of the mandible. The lesion resolved after 10 d of treatment with 1% chlorhexidine solution and triple-antibiotic ointment. However, the skin lesion subsequently recurred several times over a 2-mo period. A punch biopsy was performed, and histological changes were most consistent with a diagnosis of atopic dermatitis. Treatment with topical tacrolimus ointment, an immunosuppressive drug, proved successful in the resolution of all clinical signs after 4 mo. According to a literature review, this article is the first report of the use of tacrolimus ointment as a topical treatment of atopic dermatitis in a rhesus macaque. PMID- 19476728 TI - Acupuncture for fatigue during radiation therapy: points made. PMID- 19476724 TI - A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE). AB - OBJECTIVES: To evaluate whether the additional information provided by minimally invasive glucose monitors results in improved glycaemic control in people with poorly controlled insulin-requiring diabetes, and to assess the acceptability and health economic impact of the devices. DESIGN: A four-arm randomised controlled trial was undertaken. SETTING: Participants were recruited from secondary care diabetes clinics in four hospitals in England. PARTICIPANTS: 404 people aged over 18 years with insulin-treated diabetes mellitus (types 1 or 2) for at least 6 months who were receiving two or more injections of insulin daily were eligible. Participants had to have had two glycosylated haemoglobin (HbA1c) values > or = 7.5% in the last 15 months. INTERVENTIONS: Participants were randomised to one of four groups. Two groups received minimally invasive glucose monitoring devices [GlucoWatch Biographer or MiniMed Continuous Glucose Monitoring System (CGMS)]. These groups were compared with an attention control group (standard treatment with nurse feedback sessions at the same frequency as those in the device groups) and a standard control group (reflecting common practice in the clinical management of diabetes in the UK). MAIN OUTCOME MEASURES: Change in HbA1c from baseline to 3, 6, 12 and 18 months was the primary indicator of short- to long term efficacy in this study. Perceived acceptability of the devices was assessed by use and a self-report questionnaire. A health economic analysis was also performed. RESULTS: At 18 months all groups demonstrated a decline in HbA1c levels from baseline. Mean percentage changes in HbA1c were -1.4 for the GlucoWatch group, -4.2 for the CGMS group, -5.1 for the attention control group and -4.9 for the standard care control group. At 18 months the relative percentage reduction in HbA1c in each of the intervention arms was less than that in the standard care control group. In the intention to treat analysis no significant differences were found between any of the groups at any of the assessment times. There was no evidence that the additional information provided by the devices resulted in any change in the number or nature of treatment recommendations offered by the nurses. The health economics analysis indicated no advantage in the groups who received the devices; a lower cost and higher benefit were found for the attention control arm. Assessment of device use and acceptability indicated a decline in use of both devices, which was most marked in the GlucoWatch group by 18 months (20% still using GlucoWatch versus 57% still using the CGMS). The GlucoWatch group reported more side effects, greater interference with daily activities and more difficulty in using the device than the CGMS group. CONCLUSIONS: Continuous glucose monitors do not lead to improved clinical outcomes and are not cost-effective for improving HbA1c in unselected individuals with poorly controlled insulin-requiring diabetes. On acceptability grounds the data suggest that the GlucoWatch will not be frequently used by individuals with diabetes because of the large number of side effects. PMID- 19476730 TI - Impact of healing touch on pediatric oncology outpatients: pilot study. AB - Healing Touch (HT) is a biofield therapy used to enhance well-being. We conducted a pilot study to assess its effects in pediatric oncology patients. We enrolled patients in the continuation or consolidation phase of therapy. Patients or their parent completed simple visual analogue scales (VASs; 0-10) for relaxation, vitality, overall well-being, stress, anxiety, and depression before and after a 20-minute period of rest and a standardized HT treatment. Patients' heart rates were monitored and later analyzed for heart rate variability (HRV) characteristics. Of the nine patients, all completed VASs and six had usable HRV data. The average age was 9 years. VAS scores for stress decreased significantly more for HT treatment than for rest (HT: 4.4-1.7; rest: 2.3-2.3; p = .03). The HRV characteristic of total power was significantly lower during HT than for rest (HT 599 +/- 221; rest: 857 +/- 155; p = .048), and sympathetic activity was somewhat but not significantly lower (HT: 312 +/- 158; rest: 555 +/- 193; p = .06). HT is associated with lowered stress and changes in HRV. Further studies are needed to understand the mechanisms of these effects in larger samples and to explore the impact on additional clinically relevant measures. PMID- 19476729 TI - Pilot, randomized, modified, double-blind, placebo-controlled trial of acupuncture for cancer-related fatigue. AB - Cancer-related fatigue is a substantial problem for cancer patients and their caregivers, but no effective treatment exists. Acupuncture has been suggested to improve cancer-related fatigue, but no randomized clinical trials have been conducted. We hypothesized that true acupuncture, compared with sham acupuncture, would reduce cancer-related fatigue in cancer patients receiving external radiation therapy. The aim of this study was to determine effect size and feasibility. A modified, double-blind, randomized, placebo-controlled trial was conducted. The subject, clinical staff, and assessor were blinded, but the acupuncturist was not. Subjects received acupuncture once to twice per week during the 6-week course of radiation therapy. Data were collected at baseline, 3 weeks, 6 weeks, and 10 weeks, which was 4 weeks after that last radiation session. Twenty-seven subjects enrolled, and 23 completed the last data collection. Both true and sham acupuncture groups had improved fatigue, fatigue distress, quality of life, and depression from baseline to 10 weeks, but the differences between the groups were not statistically significant. The true acupuncture group improved 5.50 (SE, +/- 1.48) points on the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F), whereas the sham acupuncture group improved by 3.73 (SE +/- 1.92) points. This difference was not statistically significant (p = .37). All subjects guessed that they were in the true acupuncture group. Our study was underpowered to find a statistically significant difference. To demonstrate a statistically significant improvement between true and sham acupuncture would require 75 subjects per group in a future study. Owing to poor recruitment, the feasibility of a larger trial using the same methodology is low. Despite being underpowered, it appears that subjects receiving true acupuncture may benefit more than subjects receiving sham acupuncture. In the discussion section, we review our experience with using a sham-needle controlled study. PMID- 19476731 TI - Integrating a narrative medicine telephone interview with online life review education for cancer patients: lessons learned and future directions. AB - We describe an online narrative and life review education program for cancer patients and the results of a small implementation test to inform future directions for further program development and full-scale evaluation research. The intervention combined three types of psycho-oncology narrative interventions that have been shown to help patients address emotional and existential issues: (1) a physician-led dignity-enhancing telephone interview to elicit the life narrative, (2) delivery of an edited life manuscript, and (3) self-directed life review education delivered via a Web site with instructional materials and expert consultation to help people revise and share their story. Eleven cancer patients tested the intervention and provided feedback in an in-depth exit interview. Although everyone said telling and receiving the edited story manuscript was helpful and meaningful, only people with high death salience and previous computer experience used the Web tools to enhance and share their story. Computer users prodded us to provide more sophisticated tools, and older (> 70 years) users needed more staff and family support. We conclude that combining a telephone expert-led interview with online life review education can extend access to integrative oncology services, is most feasible for computer-savvy patients with advanced cancer, and must use platforms that allow patients to upload files and invite their social network. PMID- 19476732 TI - Survey of complementary and alternative medicine practitioners regarding cancer management and research. AB - The primary purpose of this survey was to assess the interest and concerns of a group of cancer complementary and alternative medicine (CAM) practitioners regarding CAM research issues. These issues include the CAM modalities used most often by CAM practitioners in the treatment of cancer patients, cancer CAM practitioners' perceptions of the most promising areas of cancer CAM research, the perceived obstacles to carrying out research objectives in the emerging field of cancer CAM research, the extent of awareness of the National Cancer Institute (NCI) Best Case Series Program, and CAM practitioners' level of interest in research collaboration with CAM researchers. A cross-sectional survey of a convenience sample of cancer CAM practitioners was conducted. One hundred thirty four respondents completed the survey. About 72% of the respondents were involved in the care of cancer patients, and these were considered the informative respondents. All results were from the informative respondent group. Respondent practitioners provided care using interventions from all seven of the predefined CAM categories. This care was provided to improve both quality of life and survival. Over two-thirds of the respondents rated research in pharmacologic and biologic treatments, alternative medical systems and nutritional therapeutics for cancer treatment, and symptom/side-effect management as high-priority areas. Although no single obstacle to research predominated as the most significant, the most frequently encountered obstacle was lack of awareness of appropriate funding sources (75.4%). More than 83% of respondents expressed some interest in or willingness to establish research collaboration with a cancer researcher. The results from this survey indicate that many cancer CAM practitioners have shared interests, perceived obstacles, and desired research opportunities. Despite a small sample size and lack of a feasible process for random sampling, this survey highlights avenues to promote and support collaborative research. The NCI/Office of Cancer Complementary and Alternative Medicine will continue to respond to the concerns elucidated by the survey by developing strategies for future program opportunities within the NCI. PMID- 19476733 TI - Phase II designs for anticancer botanicals and supplements. AB - The purpose of a phase II trial is to determine whether an anticancer agent is sufficiently promising to take forward to a definitive, randomized, phase III study. Traditional phase II trials use tumor response as an end point, defined as a 50% or greater decrease in tumor size. Anticancer botanicals and supplements are unlikely to bring about rapid tumor regression, even if they do extend survival. Accordingly, response needs to be defined in terms of survival, such as being progression-free at 6 months. Such an approach requires historical data on the expected survival rate in the absence of the botanical or supplement. We present a simple phase II design for botanicals and supplements that is based on appropriate use of historical data, incorporating adjustment for both sampling variation and case mix. The basic principle is to use a historical cohort to generate a statistical prediction model, use this to predict results of patients in the phase II study, and then compare the predictions to the observed results. Such a design asks whether patients treated by the new agent are doing better than expected; if so, this suggests that the agent should be tested further in phase III trials. PMID- 19476734 TI - Mangosteen (Garcinia mangostana). PMID- 19476738 TI - Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial. AB - Subjects diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) at biopsy are at increased risk for developing prostate cancer (CaP). A prospective clinical trial was done to determine the safety and tolerability of a novel herbal amalgam, Zyflamend (New Chapter, Inc., Brattleboro, VT), with various dietary supplements in subjects with HGPIN. Men ages 40 to 75 years with HGPIN were eligible. Subjects were evaluated for 18 months. Every 3 months, standard blood chemistries and prostate-specific antigen (PSA) were monitored. Rebiopsy was done every 6 months. Tissue was evaluated for HGPIN or CaP and stained for cyclooxygenase-2, nuclear factor kappaB (NF-kappaB), interleukin-6, and thromboxane. Twenty-three subjects were evaluable. The median age was 64.1 years (range 46-75 years), and the mean (+/- SD) PSA level was 6.13 +/- 3.56 ng/mL. Side effects, when present, were mild and gastrointestinal in nature. There were no reported serious adverse events or toxicities. No significant changes in blood chemistries, testosterone, or cardiac function were noted. Forty-eight percent of subjects demonstrated a 25 to 50% decrease in PSA after 18 months. Of subjects who had the 18-month biopsy, 60% (9 of 15) had benign tissue, 26.7% (4 of 15) had HGPIN in one core, and 13.3% (2 of 15) had CaP at 18 months. A reduction in serum C-reactive protein was observed (95% confidence interval [CI] 0.7-1.7, p = .045). Immunoreactive staining demonstrated a reduction in NF-kappaB in the 18-month samples (95% CI 0.8-3.0, p = .017). Zyflamend alone and in combination with various dietary supplements is associated with minimal toxicity and no serious adverse events when administered orally for 18 months. Further studies are warranted to evaluate these agents in patients who are at risk for CaP. PMID- 19476740 TI - beta-carboline alkaloid-enriched extract from the amazonian rain forest tree pao pereira suppresses prostate cancer cells. AB - Bark extracts from the Amazonian rain forest tree Geissospermum vellosii (pao pereira), enriched in alpha-carboline alkaloids have significant anticancer activities in certain preclinical models. Because of the predominance of prostate cancer as a cause of cancer-related morbidity and mortality for men of Western countries, we preclinically tested the in vitro and in vivo effects of a pao pereira extract against a prototypical human prostate cancer cell line, LNCaP. When added to cultured LNCaP cells, pao pereira extract significantly suppressed cell growth in a dose-dependent fashion and induced apoptosis. Immunodeficient mice heterotopically xenografted with LNCaP cells were gavaged daily with pao pereira extract or vehicle control over 6 weeks. Tumor growth was suppressed by up to 80% in some groups compared with tumors in vehicle-treated mice. However, we observed a striking U-shaped dose-response curve in which the highest dose tested (50 mg/kg/d) was much less effective in inducing tumor cell apoptosis and in reducing tumor cell proliferation and xenograft growth compared with lower doses (10 or 20 mg/kg/d). Although this study supports the idea that a pao pereira bark extract has activity against human prostate cancer, our in vivo results suggest that its potential effectiveness in prostate cancer treatment may be limited to a narrow dose range. PMID- 19476739 TI - Acupuncture for nonpalliative radiation therapy-related fatigue: feasibility study. AB - The purpose of this study was to determine the feasibility of an acupuncture clinical trial to prevent radiation therapy (RT)-induced fatigue. We conducted a cross-sectional survey study and a single-arm acupuncture clinical trial among patients undergoing RT. Patients with a Karnofsky score of less than 60, severe anemia, or substantial psychological diagnoses were excluded. Patients received up to 12 treatments of acupuncture over the entire course of their RT. The Lee Fatigue Scale (LFS) was administered at baseline, in the middle of RT, and at the end of RT, along with the Patient Global Impression of Change (PGIC). Among the 48 of 53 (91% response rate) survey participants, 20 (42%) reported that they would participate if the study were available, 13 (27%) would not participate, and 15 (31%) were unsure. Among the 16 trial participants, average fatigue and energy domains of the LFS remained stable during and after RT, without any expected statistical decline owing to RT. Based on the PGIC at the end of RT, 2 subjects (13%) reported their fatigue as worse, 8 (50%) as stable, and 6 (37%) as better. Acupuncture has the potential to prevent RT-related fatigue, which will need to be confirmed by conducting a randomized controlled trial. PMID- 19476741 TI - Maitake mushroom (Grifola frondosa): systematic review by the natural standard research collaboration. AB - The objective of this study was to evaluate the scientific evidence on maitake, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy and lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion and exclusion criteria were used for selection. Grades were assigned using an evidence-based grading rationale. There was a lack of systematic study on the safety and effectiveness of maitake in humans. However, based on popular use and supportive scientific data, three indications are discussed in this review: cancer, diabetes, and immunostimulation. Despite the lack of scientific evidence, maitake mushroom remains a popular agent in commercial products. Future randomized controlled trials are warranted. PMID- 19476743 TI - Maitake. PMID- 19476742 TI - Essiac: systematic review by the natural standard research collaboration. AB - The objective of this study was to evaluate the scientific evidence on the safety and efficacy of Essiac. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. Standardized inclusion and exclusion criteria were used for selection. A review of the literature on Essiac and essiac formulations showed a lack of high-quality clinical trials to substantiate any of Essiac's traditional uses. Weak evidence from preclinical, animal, and laboratory data warranted a discussion regarding Essiac's use for cancer, but the results are inconclusive. Several other essiac preparations are noted in the literature, adding confusion to the exact formula and its proposed benefits. In general, there is a lack of both safety and efficacy data for Essiac and essiac formulations. Well-designed trials testing Essiac or individual herbal components are necessary to make firm recommendations. PMID- 19476744 TI - Complex abdominal aortic pathologies: operative and midterm results after pararenal aortic aneurysm and type IV thoracoabdominal aneurysm repair. AB - The aim of the study was to describe the clinical outcome of pararenal aortic aneurysm (PAAA) and type IV thoracoabdominal aneurysm (TAAA) repair, with special consideration placed on disease-related complications and midterm follow-up. Data were collected retrospectively between 1997 and 2004 for patients with PAAA or type IV TAAA repair. Comorbidities, operative details, and early and late outcome were analyzed to predict disease-related complications. During the study period, 63 patients (33 PAAAs, 30 type IV TAAAs) underwent aortic repair. The 30-day mortality rate of 7.9% was acceptable for complex aortic entities compared with other series. The morbidity for cardiac events was 3.2%, for pulmonary complications 17.5%, and the need for reoperation was 14.3%. With regard to disease-related complications, two patients (3.2%) required dialysis and one patient (1.6%) developed paraplegia (spinal cord ischemia) after type IV TAAA repair. Complex aortic repair for PAAAs and type IV TAAAs showed acceptable perioperative mortality, morbidity, and midterm survival rates. Patients with type IV TAAAs suffered more major complications, such as postoperative dialysis or spinal cord ischemia. PMID- 19476745 TI - Can laboratory tests predict the prognosis of patients after endovascular aneurysm repair? Current status and future directions. AB - The purpose of this study was to determine what laboratory values predict the prognosis of patients after endovascular aneurysm repair (EVAR). MEDLINE and Cochrane Library databases were searched. This resulted in 13 relevant articles. Data were pooled, and meta-analyses were performed. A meta-analysis including 5,655 patients showed that preoperative serum creatinine>1.5 mg/dL was a significant risk indicator for increased 30-day mortality (relative risk 3.0, 95% confidence interval 2.3-4.1, p<.0001). Four other studies showed that other cutoff values of creatinine or glomerular filtration rate can predict mortality and complications following EVAR. One study suggested that reduced preoperative hemoglobin is a risk indicator for reduced long-term survival. Increased serum creatinine, reduced glomerular filtration rate, and reduced hemoglobin are significant and strong predictors of mortality and complications after EVAR. Current evidence remains limited, and further research is needed to determine conclusively additional laboratory values that may predict the outcome of patients following EVAR. PMID- 19476746 TI - Endovascular management of takayasu arteritis: is it a durable option? AB - Interim outcome of endovascular management of Takayasu arteritis (TA) was determined retrospectively to assess the efficacy of angioplasty and/or stenting in 24 patients with 35 lesions in the chronic inactive stage. The renal (n=16), subclavian/innominate (n=11), and carotid (n=5) arteries and abdominal aorta (n=3) were treated. Twenty-six lesions achieved excellent to good target lesion revascularization with no residual or only minimal residual stenosis, whereas five had a moderate result. Thirty lesions achieved satisfactory hemodynamic correction. Restenosis was observed in 8 lesions treated with angioplasty alone (n=18) and in 3 lesions treated with angioplasty and stenting (n=17). All recurrent stenoses underwent successful reintervention without significant complication. Treatment of inactive stage TA lesions with angioplasty alone or with angioplasty and stenting results in excellent to good clinical improvement in the majority of patients (follow-up at 46.8 months). Endovascular therapy is a durable treatment option in patients with chronic inactive stage TA. PMID- 19476749 TI - Truncus bicaroticus and an aberrant right subclavian artery contributing to internal jugular venous line misplacement into the carotid artery. AB - Truncus bicaroticus, or common origin of the carotid arteries, is extremely rare and has been described sparsely in the literature. It has been reported as an incidental finding during cadaveric dissection and as an anatomic variant found during routine angiography. We report the case of a 75-year-old woman with a previously unknown truncus bicaroticus and an aberrant right subclavian artery in whom the anatomic variations contributed to an arterially placed central venous catheter remaining undetected. This catheter misplacement was suspected after the patient developed an embolic stroke, and subsequent studies demonstrated the truncus bicaroticus and intra-arterial catheter placement. To our knowledge, this is the first case reporting a truncus bicaroticus associated with an aberrant right subclavian artery. PMID- 19476748 TI - Autologous basilic vein for in situ replacement of infected prosthetic vascular grafts: initial experience. AB - Successful treatment of prosthetic vascular infection usually requires graft removal with or without replacement. A variety of materials have been used for in situ replacement, with femoral vein being the preferred autologous conduit in the literature for the aortoiliac segment. We present three cases of prosthetic infection treated successfully by in situ replacement with autologous basilic vein harvested from the upper arm. This vessel, which closely matches the iliofemoral arteries in diameter, may be a suitable alternative to femoral vein for in situ replacement of infected iliac and femoral grafts. PMID- 19476747 TI - Thoracic aortic dissection: are matrix metalloproteinases involved? AB - Thoracic aortic dissection, one of the major diseases affecting the aorta, carries a very high mortality rate. Improving our understanding of the pathobiology of this disease may help us develop medical treatments to prevent dissection and subsequent aneurysm formation and rupture. Dissection is associated with degeneration of the aortic media. Recent studies have shown increased expression and activation of a family of proteolytic enzymes-called matrix metalloproteinases (MMPs)-in dissected aortic tissue, suggesting that MMPs may play a major role in this disease. Inhibition of MMPs may be beneficial in reducing MMP-mediated aortic damage associated with dissection. This article reviews the recent literature and summarizes our current understanding of the role of MMPs in the pathobiology of thoracic aortic dissection. The potential importance of MMP inhibition as a future treatment of aortic dissection is also discussed. PMID- 19476750 TI - Mycotic pseudoaneurysm of the superficial femoral artery in a patient with Cushing disease: case report and literature review. AB - Mycotic pseudoaneurysms of the peripheral arteries are rare and can occur as an extension of localized infection or from systemic sepsis. In some cases, no obvious source of infection may be identified. Both endovascular and open surgical management options are available for this important condition. We report a mycotic pseudoaneurysm of the superficial femoral artery in a patient associated with systemic immunosuppression secondary to Cushing disease that was successfully managed with open surgical repair and autologous bypass grafting. This unusual case highlights the potential for serious adverse cardiovascular sequelae of Cushing disease and the need for awareness of such complications in this patient group. PMID- 19476751 TI - Upper gastrointestinal obstruction secondary to aortoduodenal syndrome owing to a noninflammatory abdominal aortic aneurysm. AB - Aortoduodenal syndrome is a rare complication of an abdominal aortic aneurysm wherein the aneurysm sac obstructs the patient's duodenum. It presents with the symptoms of an upper gastrointestinal tract obstruction and requires surgical intervention to relieve it. Previously, gastric bypass surgery was advocated, but now aortic replacement is the mainstay of treatment. We report a case of a 67 year-old woman whose aortoduodenal syndrome was successfully managed and review the literature on this topic. PMID- 19476753 TI - Aortic angiosarcoma with cutaneous metastases. AB - Primary aortic tumors are rare and include a variety of histologic types, including aortic angiosarcomas, with less than 100 cases being reported since the first description of these tumors in 1873. The diagnosis of aortic angiosarcoma is usually confirmed by postoperative histopathologic examination or postmortem study. We present a case of primary aortic angiosarcoma presenting with intermittent claudication and radiologic findings of aortoiliac atherosclerotic disease treated initially with stenting; lower extremity embolic skin metastases developed during follow-up that prompted resection of the aortic bifurcation and restoration of the arterial continuity with a bypass. Despite postresection recurrence, a 3-year survival was achieved with aggressive multidisciplinary management. PMID- 19476755 TI - Endoscopic resection of pterygopalatine chondrosarcoma. PMID- 19476752 TI - Combined supra-aortic extra-anatomic revascularization and endovascular hybrid procedure for recurrent hemoptysis caused by a symptomatic aneurysm of the right subclavian artery. AB - Acute hemoptysis might be caused by aneurysms of the subclavian artery. We report a 75-year-old female patient presenting with recurrent hemoptysis, dyspnea, fever, and episodes of unclear pneumonia. Further examination revealed a large intrathoracic aneurysm of the right subclavian artery. After an initial transfemoral interventional attempt to occlude the entry of the aneurysm, the patient developed persistent thoracic pain. The patient was then treated by a combined extrathoracic hybrid procedure with a left to right carotid-carotid axillary artery bypass and an endovascular aneurysm exclusion by insertion of two iliac artery occluder stent grafts in the proximal brachiocephalic trunk and the distal right subclavian artery. After this combined intervention, hemoptysis disappeared, and the patient recovered remarkably during a follow-up of 24 months. PMID- 19476756 TI - Inflammatory myofibroblastic tumour of the subglottis in a 5-year-old. PMID- 19476758 TI - Acanthamoeba rhinosinusitis. PMID- 19476757 TI - Cysticercosis: a rare cause of orbital infection. PMID- 19476759 TI - Carcinoid tumours of the middle ear. PMID- 19476760 TI - Hearing loss owing to intralabyrinthine schwannoma responsive to intratympanic steroid treatment. PMID- 19476761 TI - Two cases of nasopharyngeal stenosis after multiple adenoidectomies. PMID- 19476762 TI - Tympanomastoidectomy: planned second-look tympanotomy. AB - OBJECTIVE: To review the outcome following surgery for cholesteatoma/retraction pocket disease where second-look tympanotomy was recommended for selected patients. DESIGN: Retrospective outcome analysis following canal wall down mastoid surgery for cholesteatoma/retraction pocket disease. SUBJECTS: The study included 158 patients (163 ears) operated on between 1993 and 2003. Data were collected on the recommendation for second-look tympanotomy, the findings at second-look tympanotomy, and hearing threshold. RESULTS: Second-look tympanotomy was recommended for 36 patients, 32 had surgery, and 30 were free of residual disease. The respective mean pre- and postoperative bone conduction threshold was 8.9 dB and 18 dB for single-stage surgery and 15.8 dB and 16.8 dB for second-look tympanotomy. The mean preoperative air-bone gap (0.5, 1, 2, 4 kHz) was 27.1 dB for single-stage surgery and 27.9 dB for staged surgery. The 1-year air-bone gap was 24.6 dB and 28.6 dB, respectively. CONCLUSION: Planned second-look tympanotomy demonstrated excellent early disease control and allowed management of the middle ear pathology. PMID- 19476763 TI - Comparison of three methods of testing hearing in mice. AB - INTRODUCTION: This study compares the reliability and validity of three methods of testing hearing in mice. SETTING: Animal research laboratory. METHODS: Three methods of testing hearing were used in 18 mice: (1) auditory brainstem response (ABR), (2) electrocochleography with a needle electrode, and (3) electrocochleography with a soft, cotton-wick electrode. RESULTS: Reliability was good for all three tests, but ABR testing was the easiest and provided the lowest thresholds and least variability. The results for these tests under other conditions may vary. CONCLUSION: ABR testing can be considered an optimal test method under the circumstances in this study. PMID- 19476764 TI - Dystrophic pathology in the intrinsic and extrinsic laryngeal muscles in the mdx mouse. AB - OBJECTIVE: This study aimed to characterize the laryngeal muscles in the mdx mouse model of Duchenne muscular dystrophy (DMD). DESIGN: Pathology was analyzed in the intrinsic and extrinsic laryngeal muscles from mdx mice and compared with other mdx muscle groups and with muscles from age-matched normal control mice. SETTING: In DMD, a dystrophin protein deficiency causes skeletal muscle breakdown. However, some muscle groups, such as the extraocular muscles, are spared from damage. Characterizing other unaffected muscles may form the basis for developing new therapies to alleviate muscle breakdown in DMD. METHODS: Extraocular, diaphragm, tibialis anterior, intrinsic laryngeal, and extrinsic laryngeal muscles were collected from normal (C57Bl/10ScSn) and dystrophic (mdx) mice and analyzed histopathologically. MAIN OUTCOME MEASURES: The extent of pathology was determined by analyzing centrally nucleated muscle fibres, the percentage of necrotic tissue, and uptake of Evan's blue dye into muscle fibres. Expression levels of dystrophin and its related proteins, beta-dystroglycan, utrophin, and caveolin-3, were analyzed by immunofluorescence. RESULTS: The mdx cricothyroid and extrinsic laryngeal muscles had levels of pathology similar to those of the diaphragm and hindlimb muscles, whereas the remaining intrinsic laryngeal muscles showed very mild pathology. Expression of dystrophin, beta dystroglycan, and utrophin did not differ between mdx muscle groups. Although caveolin-3 was upregulated in all mdx muscles compared with those from normal mice, this upregulation was significantly higher in the mdx extraocular muscles. CONCLUSIONS: With the exception of the cricothyroid, the intrinsic laryngeal muscles may be useful for comparison with the extraocular muscles to identify characteristics that spare them from disease pathology despite a dystrophin deficiency. PMID- 19476765 TI - Surgical anatomy of the spinal accessory nerve: is the great auricular point reliable? AB - OBJECTIVE: The study was to exam if the great auricular point is a dependable landmark for finding the spinal accessory nerve. DESIGN: A prospective study from January 2004 to August 2006 in a tertiary medical centre. SETTING: A tertiary medical centre, Tzu Chi General Hospital. METHODS: In the modified radical neck dissection, the topographic anatomy of spinal accessory was studied in 50 patients. MAIN OUTCOME: The great auricular point (GAP) was identified and the length of sternocleidomastoid muscle (SCM) below was measured. The distance between the spinal accessory nerve and the greater auricular point was measured. RESULTS: The ratio of the length of the SCM below the nerve exiting point to the total length of the muscle was near 0.66. The mean distance between the GAP and the accessory nerve was 0.92 cm (SD +/- 0.27). CONCLUSIONS: The great auricular point is a reliable landmark for identification of the accessory nerve during the neck dissection. PMID- 19476766 TI - Retrospective study of the long-term results of otoplasty using a modified Mustarde (cartilage-sparing) technique. AB - OBJECTIVE: To determine the long-term results and the complication rates of a cartilage-sparing otoplasty technique. PATIENTS AND METHODS: In our study, patients who had undergone otoplasty from 1990 to 2002 inclusively were evaluated retrospectively. The study consisted of a chart review and a telephone survey. The minimum follow-up for patients was 5 years. MAIN OUTCOME MEASURES: The main outcome measures were long-term satisfaction rates, early complications, late complications, and rate of revisional procedures. A detailed description of the surgical technique is included. RESULTS: The overall long-term satisfaction rate was 95.7%. Early complications (< 1 month) included one case of bleeding (1.0%) and five cases of asymmetry (4.9%) between both ears, two of which required reoperations. One case of early unilateral recurrence was noted owing to trauma inflicted by another child (1.0%) and necessitated a revisional procedure. Late complications (> 1 month) included five cases (4.8%) of suture granulomas/extrusions, three (2.9%) keloids, and one case of hypertrophic scarring (1.0%). Seven cases of partial recurrence of the deformity (10.3%) were noted, six of which were unilateral and one of which was bilateral, none requiring reoperation. There was only one case of overcorrection of the deformity (1.4%). Three cases within the sample of 104 patients underwent reoperation, yielding a 2.9% rate of revision procedures. CONCLUSIONS: On long-term follow-up, the otoplasty technique used in our institution yields a high satisfaction rate and a low complication rate. PMID- 19476767 TI - Fine-needle aspiration biopsy of the thyroid: review of cytopathologic features predictive of malignancy. AB - OBJECTIVE: To determine the value of specific cytopathologic features on fine needle aspiration biopsies (FNABs) at predicting thyroid malignancy. DESIGN: Retrospective review of consecutive patients undergoing thyroidectomy between 2005 and 2007 following FNAB of thyroid nodules. SETTING: Two McGill University teaching hospitals in Montreal. METHODS: One hundred forty-seven patients were reviewed and further categorized into two groups (benign vs malignant) based on the final histopathologic diagnosis. The frequency of specific cytopathologic features from the preoperative FNAB samples was recorded for 106 patients from the first hospital and 41 patients from the second. RESULTS: The presence of atypical cells (30% vs 72%; p = 3.23 x 10(-7)), nuclear grooves (5% vs 23%; p = .002), anisonucleosis (8% vs 36%; p = .00011), variable chromatin staining (10% vs 28%; p = .007), hypochromasia (11% vs 47%; p = 7.19 x 10(-6)), nuclear overlapping/crowding (8% vs 29%; p = .0019), irregular nuclear membranes (15% vs 52%, p = 3.22 x 10(-6)), micronucleoli (15% vs 60%, p = .003), and powdery chromatin (8% vs 47%, p = .004) correlates with an increased risk of malignancy. Alternatively, siderophages (44% vs 23%; p = .007) and honeycomb arrangements (92% vs 60%; p = .012) were more associated with benign processes. HBME-1 staining (n = 53) was positive or focally positive on 61% of the malignant cases (p = .0002), with a specificity of 100%. All biopsies demonstrating intranuclear inclusions, papillary fragments, or atypical architecture were malignant. CONCLUSION: Some cytopathologic features are more significantly associated with thyroid malignancy. The cytopathologic features listed in FNAB reports and HBME-1 immunoreactivity are, alone or in combination, additional tools available to the physician to guide management of thyroid nodules. PMID- 19476769 TI - Cartilage tympanoplasty: indications, techniques, and results. AB - OBJECTIVE: To present our experience with cartilage grafts in ear surgery and review the indications and techniques. DESIGN: Retrospective clinical evaluation. SETTING: There were 25 ears of 23 patients in our series, with a mean follow-up of 24.7 months (range 12-53). METHODS: The surgeries were eight type I tympanoplasties, four type III tympanoplasties without mastoidectomy, and four canal wall up and nine canal wall down tympanomastoidectomies with ossicular reconstruction. Nine total ossicular replacement prostheses and eight partial ossicular replacement prostheses were used in the ossicular reconstructions. Fourteen cartilage grafts were harvested from the concha and 11 from the tragus; the grafting technique was total cartilage plate in 18 ears, cartilage shield in 6 ears, and palisade in 1 ear. MAIN OUTCOME MEASURES: Otomicroscopic, otoendoscopic, and audiologic examinations before and after the surgeries. RESULTS: There were no cases of graft loss, and no perforations were observed. The postoperative hearing was stable in 9 ears (36%) and improved in 16 ears (64%), with a mean postoperative hearing gain of 20 dB (range 10-40 dB). We concluded that cartilage grafts are ideal in cases of retraction and adhesion, as well as sclerosis, atrophy, and infection. CONCLUSIONS: Cartilage can be used as a total, shield, or palisade graft in ear surgery. These grafts are stable and reliable, and the postoperative hearing results are as good as or even better than fascia grafting. PMID- 19476768 TI - Complementary and alternative medicine use among patients undergoing otolaryngologic surgery. AB - OBJECTIVE: The use of complementary and alternative medicine (CAM) may influence surgical care by inducing coagulopathies and interacting with other medication. We investigated the prevalence and pattern of CAM use in patients admitted to our department for elective otolaryngologic surgery. DESIGN: Cross-sectional survey. SETTING: Tertiary care referral centre in northeast Scotland. METHOD AND PATIENTS: All adult patients admitted for elective surgery, over a 14-week period from October 2005 to January 2006, were requested to complete an anonymous questionnaire. Data were analyzed with descriptive statistics using SPSS version 12 (SPSS Inc, Chicago, IL). MAIN OUTCOME MEASURES: To establish the prevalence of CAM use in patients admitted for surgery in our unit. Secondary measures included the type of CAM used, indications for use, perceived benefit, and communication with the family physician. RESULTS: Sixty-three percent (177 of 285) of the patient group had used CAM-36% in the preceding year. Popular remedies were cod liver oil, garlic, aloe vera, cranberry, echinacea, primrose oil, herbal vitamin supplement, and St. John's wort. Nonherbal therapies included massage, acupuncture, chiropractic, aromatherapy, reflexology, yoga, homeopathy, and osteopathy. Nine percent used CAM for their admission illness. Only 8% (15 of 177) found CAM ineffective. Only 76 of 177 (43%) had discussed their CAM use with their family doctor. CONCLUSION: Despite concerns over its safety, efficacy, and cost-effectiveness, the use of CAM is common among patients undergoing otolaryngologic and head and neck surgery. This has implications for all health care workers involved in their care, in particular the anesthetist and the surgeon. A detailed history of CAM use by patients should be taken and documented during the preoperative clerking. PMID- 19476770 TI - Informed consent in rhinoplasty: prospective randomized study of risk recall in patients who are given written disclosure of risks versus traditional oral discussion groups. AB - OBJECTIVE: To determine the effectiveness of providing written information in enhancing patient understanding and retention. DESIGN: A multicentre prospective randomized study was conducted in university-affiliated ambulatory surgical centres. One hundred consecutive patients seen for rhinoplasty consultation were included. Patients were randomly assigned to (1) those receiving traditional oral dialogue of the surgical risks or (2) those receiving an oral discussion and a written pamphlet outlining the risks of the procedure. Fourteen to 18 days after the consultation, each patient was contacted for an assessment of risk recall. RESULTS: Overall risk recall was higher in the group that received written information (2.3 vs 1.3 of 5 risks; p < .008). As well, in the group that received a pamphlet, patients with university and postgraduate levels of education had a better rate of recall (p < .05). Female patients in both groups reported higher risk recall (p < .01). CONCLUSION: Patient risk recall of rhinoplasty is improved with the addition of written information during the informed consent process. As the process of informed consent plays a very decisive role in facial plastic surgery, enhanced postoperative satisfaction may result from the use of supplemental educational materials. PMID- 19476771 TI - Dizziness in patients with recent episodes of benign paroxysmal positional vertigo: real otolithic dysfunction or mental stress? AB - OBJECTIVE: Our goal was to verify the existence of otolithic dysfunction or mental stress in patients with dizziness following an episode of benign paroxysmal positional vertigo (BPPV) that was treated and resolved. STUDY DESIGN: Prospective study. METHODS: Forty patients with BPPV were examined 2, 7, and 14 days after resolution. Based on residual symptoms reported during three follow ups, they were classified as type A (with dizziness) or type B (without dizziness). During the first follow-up, they were asked to compile a self-rating anxiety scale (SAS), and we then determined subjective visual vertical (SVV). The determination of SVV was repeated during the subsequent follow-ups. For each patient, we also evaluated the rate of BPPV episodes that were recurrent and resistant to treatment and examined distribution by age and gender during the follow-ups. RESULTS: A comparison of type A (1.20 +/- 0.45) and type B (0.64 +/- 0.58) patients showed a significant difference in determining SVV only at the first follow-up (p = .002). Among type A patients, the rate of resistant BPPV was 75%, whereas the rate of recurrent BPPV was 100% at the third follow-up, during which the SAS revealed a significant increase (p = .005) among type A (52 +/- 3.74) versus type B (41.6 +/- 4.7) patients; the male to female ratio was 1:5 (type A) and 4:5 (type B), and the mean ages were, respectively, 56.4 +/- 4.98 and 43.6 +/- 10.2. CONCLUSIONS: Otolithic dysfunction explains only brief dizziness. The persistence of dizziness is correlated with mental stress that is affected by the duration and recurrence of BPPV, age, and gender. PMID- 19476772 TI - Quantitative proteomics of nasal mucus in chronic sinusitis with nasal polyposis. AB - BACKGROUND: Proteomics has been used as a tool for identification of the protein content of nasal mucus in diseased and healthy subjects. Thirty-five proteins in both chronic rhinosinusitis (CRS) and control groups were identified in a previous study by our group using conventional mass spectrometry analysis. Ten of these proteins were related to innate and acquired immunity and showed differences in expression between the two groups. OBJECTIVE: To investigate the quantitative differential expression of specific nasal mucus proteins previously identified by our group using multiple reaction monitoring (MRM) mass spectrometry in patients with CRS with nasal polyposis compared with normal subjects. METHODS: In a prospective case control study, nasal mucus from patients and control subjects was collected, desalted, resolubilized, and digested using proteolytic enzymes. Previously identified nasal mucus proteins with differential expression in CRS patients were targeted and quantitatively measured using MRM mass spectrometry. RESULTS: Analysis of 12 samples (6 patients and 6 controls) identified 7 of the 10 targeted proteins, many of which were related to innate and acquired immunity. Quantitative analysis showed differential expression in CRS patients compared with control subjects. A detailed analysis and characterization of the protein isolates is outlined. CONCLUSION: This is the first proteomics study of nasal mucus in CRS with polyposis using the MRM technique. The findings suggest that innate and acquired immunity may play a role in the pathophysiology of CRS. Future steps in evaluating the protein characteristics of the mucus of CRS patients are aimed at developing biomarkers and potentially targeted therapies. PMID- 19476773 TI - Short-term results of endonasal dacryocystorhinostomy with a mucosal flap and a bone dissection technique. AB - OBJECTIVE: To determine the short-term results of endonasal dacryocystorhinostomy (DCR) with a mucosal flap and a bone dissection technique. MATERIALS AND METHODS: A retrospective study including consecutive 22 patients who underwent endonasal DCR between June 2004 and January 2006. The study was designed to look at the patients' symptoms and satisfaction following the procedure; hence, a telephone survey was undertaken. The absence or improvement of symptoms was defined as a successful outcome. RESULTS: There were 22 patients in the study cohort. The mean follow-up was 12 months. The procedure was successful in 20 patients (90.9%), with no residual epiphora. Failure was noted only in 2 patients. CONCLUSION: The short-term success rate of endonasal DCR was 90.90%. In a previous study from our unit, the success rate with endonasal laser DCR at 1 year was 83% and the 5-year success rate was only 56%, which made us stop doing the laser approach. We currently favour endonasal DCR with the mucosal flap approach in our unit. PMID- 19476774 TI - Predictors of malignancy in preoperative nondiagnostic biopsies of the thyroid. AB - OBJECTIVE: To determine whether preoperative variables can be used to predict malignancy for thyroid nodules with follicular, Hurthle, or nondiagnostic cytology on fine-needle aspiration biopsy (FNAB). MATERIALS AND METHODS: Retrospective analysis of 77 consecutive patients selected for total or subtotal thyroidectomy for follicular, Hurthle, or nondiagnostic lesions of the thyroid in two university hospitals. Eleven clinical variables, as well as nodule size, multiplicity, and ultrasound calcifications, were correlated with final histopathologic diagnosis of benign or malignant disease. Analysis was preformed using the Pearson chi-square test. RESULTS: The overall rate of malignancy in our series was 61% (n = 47). FNABs classified as follicular or Hurthle lesions without cellular atypia had a significantly lower risk of malignancy (49% vs 71%; p = .05). Patients who presented with a solitary nodule and FNAB cellular atypia displayed an increased risk of malignancy (92% vs 55%; p = .011). The rate of malignancy was higher for patients with a positive family history (100% vs 59%), a solitary nodule (73% vs 53%), cellular atypia (76% vs 54%), or intrathyroidal calcifications on ultrasonography (71% vs 57%), although none were found to be statistically significant (p > .05). Male gender, age > 45 years, nodule size > 3 cm, mass effect symptoms, and radiation exposure to the neck were not associated with malignancy in our series. CONCLUSION: When presented with follicular, Hurthle, or nondiagnostic biopsies for thyroid nodules, thyroid surgeons should rely systematically on sonographic findings and cytopathologic features to guide their management approach. PMID- 19476776 TI - Cochlear nerve aplasia detected through kindergarten hearing screening. AB - OBJECTIVES: To describe the importance of imaging with the use of magnetic resonance (MR) or computed tomography (CT) during the diagnostic workup of a patient with sensorineural hearing loss to determine the status of the cochlear nerve. DESIGN: Retrospective review. SETTING: Tertiary care academic institution. METHODS: A pediatric database was used to find patients with diagnoses of absent cochlear nerve. A retrospective chart review was performed from July 1999 to July 2004 to evaluate the route to diagnosis and any concomitant factors. Patients who had presented at kindergarten screening were included. Review was made of the audiologic investigations undertaken: routine audiometry, auditory brainstem response (ABR), and distortion product otoacoustic emission (OAE). Radiologic investigations were also reviewed consisting of CT and/or MR scans. RESULTS: The database yielded 12 cases of cochlear agenesis. Four patients were excluded because they had absence of the entire inner ear structures ipsilateral to the aplastic cochlear nerve (two cases) and because they had multiple congenital anomalies (two cases). There were equal numbers of males and females. There was a slight left-sided preponderance (5:3), and ages ranged from 5 through 7 years. All children had failed the initial screening audiogram. Follow-up audiologic evaluation revealed either profound loss or dead ear or a failed ABR in the presence of normal OAE testing. All patients had internal auditory canals less than 1.4 mm or MR-compatible findings. CONCLUSIONS: Agenesis of the cochlear nerve may be more common than previously thought, especially in an otherwise healthy, nonsyndromic, school-aged child. Although audiometric evaluation alone usually strongly suggests the diagnosis, definitive evaluation with MR remains the gold standard. PMID- 19476775 TI - Quality of life after oral and oropharyngeal reconstruction with a radial forearm free flap: prospective study. AB - OBJECTIVE: To evaluate quality of life (QOL) after radial forearm free flap (RFFF) reconstruction of the oral cavity and oropharynx in head and neck cancer patients. DESIGN: Prospective study. SETTING: Academic, tertiary referral centre. METHODS: Between January 2004 and May 2005, 47 patients underwent immediate RFFF reconstruction of the oral cavity and oropharynx following ablative surgery for a previously untreated head and neck cancer and were initially included in this study. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Head and Neck Cancer Quality of Life Questionnaire were completed before surgery and at 6 and 12 months thereafter. MAIN OUTCOME MEASURES: QOL scores obtained at the three assessment dates. Predictive factors of QOL scores at 6 months researched among the following: age, gender, comorbidity, radiotherapy, tumour stage, and tumour site. RESULTS: Global QOL remained stable over time. Social and role functioning scores deteriorated significantly after treatment. Social eating and speech difficulties, trismus, and salivary problems increased significantly in the postoperative period and were among the main complaints of our patients. CONCLUSIONS: Despite some functional impairment, global QOL was preserved after RFFF reconstruction following extensive ablative surgery in patients with oral and oropharyngeal cancer. PMID- 19476777 TI - Areola-sparing techniques for breast malignancies with nipple discharge. PMID- 19476780 TI - Transcervical superior mediastinal lymph node dissection combined with transhiatal lower esophageal dissection before transthoracic esophagectomy: a safe approach for salvage esophagectomy. PMID- 19476782 TI - Emergency traumatologists as partners in trauma care: the future is now. AB - BACKGROUND: Decreasing manpower available to care for trauma patients both in and out of the ICU has led to a number of proposed solutions, including increasing involvement of emergency medicine-trained physicians in the care of these patients. We performed a descriptive comparative study in an effort to define the role of fellowship-trained emergency medicine physicians as full-time traumatologists. STUDY DESIGN: We performed a retrospective review of concurrent and prospectively collected data comparing process of care and outcomes for the resuscitative phase of trauma patients cared for by full-time fellowship-trained trauma surgeons (TS), a fellowship-trained emergency medicine physician (ET), and a first-year fellowship-trained trauma surgeon (TS1). RESULTS: Patient age, Revised Trauma Score, and Injury Severity Score were similar between groups. Process of care, defined by transfusion of uncrossmatched blood, prevalence of hypotension in patients receiving uncrossmatched blood, time spent in the emergency department, frequency of ICU admission, severity of injury for ICU admission, and time between emergency department and operating room for patients requiring surgery, was equivalent between groups. Outcomes evaluated by mortality and length of stay in the hospital and ICU did not differ between groups, and provider group was not predictive of mortality in stepwise logistic regression. CONCLUSIONS: These data suggest that emergency traumatologists can provide trauma care effectively within a defined scope of practice and may provide an effective solution to manpower issues confronting trauma centers. PMID- 19476783 TI - Endovascular treatment of traumatic thoracic aortic injuries. AB - BACKGROUND: Although a large proportion of patients with traumatic thoracic aortic injury die before undergoing definitive repair, those who survive still face ongoing risk of death and morbidity. Endovascular therapy may offer a minimally invasive alternative in the repair of the aortic injury. STUDY DESIGN: We reviewed our experience with endovascular repair of traumatic aortic injuries using medical records, imaging studies, and a prospectively maintained endovascular and institutional trauma database. RESULTS: Twenty-two patients underwent thoracic endovascular repair (TEVAR) of traumatic aortic injuries over 44 months. The mean (SD) age was 34+/-12 years and 68% were men. Among the 16 patients registered with our trauma database, the mean Injury Severity Score was 33+/-16 (range, 13 to 45). All injuries were sustained from blunt trauma; 95% of patients had nonaortic thoracic injuries, and 64% and 55% had extremity and abdominal injuries, respectively. Intraoperatively, 91% were repaired under general anesthesia, the mean procedure time was 80+/-52 minutes, and mean blood loss was 219+/-72 mL. The mean fluoroscopy time was 13+/-5 minutes and contrast volume 98+/-23 mL. Twenty-one patients (95%) required coverage of the left subclavian artery to achieve an adequate proximal landing zone. There were no in hospital or 30-day deaths. The median length of stay was 8 days (range, 1 to 62 days), and 11 (50%) patients were able to be discharged home (versus to another extended care facility). At a mean followup of 7.7 months (range, 0 to 40 months) there were 2 patients (9%) who required endograft-related reintervention at 1 and 6 months. One was an access-related complication, and the second was complete device collapse with acute aortic occlusion, resulting in the patient's death. CONCLUSIONS: Although patients who undergo endovascular repair of traumatic thoracic aortic transections typically have significant concomitant injuries, the procedure itself is well tolerated and can be performed rapidly with minimal blood loss and contrast administration. But close followup is necessary given the risk of late complications. PMID- 19476784 TI - Is routine postoperative chest x-ray necessary after fluoroscopic-guided subclavian central venous port placement? AB - BACKGROUND: Two uncommon but serious complications after subclavian central venous port (SCVP) placement are pneumothorax (PNX) and malposition of the catheter. Chest x-rays (CXR) are commonly obtained after SCVP placement to identify these complications, but their use is controversial. STUDY DESIGN: We performed a retrospective review of SCVP placements to establish the incidence of PNX or catheter malposition identified exclusively by postprocedure CXR. RESULTS: Between July 1, 2001, and June 30, 2006, 205 patients underwent elective SCVP placement. Although 4 patients (2%) sustained a PNX, none was identified by routine postprocedure CXR. Postprocedure clinical symptoms (3 to 72 hours later) prompted repeat CXR, which identified the PNX. Five patients (2.4%) had catheter malposition recognized by intraoperative fluoroscopy and corrected intraoperatively. No malpositioned catheters were identified on postprocedure CXR. CONCLUSIONS: In our study, incidence of PNX after SCVP placement was low, and PNX was not detected by intraoperative fluoroscopy or by routine postprocedure CXR. We conclude that the practice of routine postprocedure CXR after SCVP placement is not necessary and should be replaced with diagnostic chest radiography only if symptoms develop. PMID- 19476781 TI - Modulation of the hypermetabolic response to trauma: temperature, nutrition, and drugs. PMID- 19476785 TI - Relationship between hospital volume, system clinical resources, and mortality in pancreatic resection. AB - BACKGROUND: The relationship between hospital volume and perioperative mortality in pancreaticoduodenectomy has been well established. We studied whether associations exist between hospital volume and hospital clinical resources and between both of these factors to mortality to help explain this relationship. STUDY DESIGN: This two-part study reviewed publicly available hospital information from the Leapfrog Group, HealthGrades, and hospital Web sites. Hospitals were evaluated for Leapfrog ICU staffing criteria and Safe Practice Score; HealthGrades five-star rating for complex gastrointestinal procedures and operations; and presence of a general surgery residency, gastroenterology fellowship, and interventional radiology. Evaluation used trend analysis and multiple logistic regression analysis. The second part determined the mortality rate for pancreaticoduodenectomy using inpatient mortality data from the National Inpatient Sample and Leapfrog. Hospitals were categorized by low volume (< or = 10/year), high volume (> or = 11/year), strong clinical support (presence of all support factors), and weak clinical support (absence of any factor). Data were correlated by number of pancreatic resections per hospital, hospital system clinical resources, and operative mortality. RESULTS: As hospital volume increased, statistically significant increases occurred in the frequency of hospitals meeting Leapfrog ICU staffing criteria (p < 0.0001), Leapfrog Safe Practice Score (p = 0.0004), HealthGrades 5-star rating (p < 0.00001), general surgery residency (p < 0.00001), gastroenterology fellowship (p < 0.00001), and interventional radiology services (p < 0.00001). No significant relationships were found between resection volume and any one of the clinical support factors and perioperative death. Presence of strong clinical support was associated with lower mortality (odds ratio = 0.32; p = 0.001). CONCLUSIONS: System clinical resources were more influential in operative mortality for pancreatic resection. This might help explain why high-volume hospitals, low-volume surgeons in high volume institutions, and some lower-volume hospitals with excellent clinical resources have lower perioperative mortality rates for pancreatic resection. PMID- 19476786 TI - The volume-outcomes effect in hepato-pancreato-biliary surgery: hospital versus surgeon contributions and specificity of the relationship. AB - BACKGROUND: Although the relationship between hepato-pancreato-biliary (HPB) procedure volume and outcomes is established, the relative importance of hospital and surgeon effects and the specificity of the volume-outcomes effect remain ill defined. We sought to comprehensively characterize the hospital and surgeon volume-outcomes relationships in high-risk HPB surgery. STUDY DESIGN: The 1998 to 2005 State Inpatient Databases for Florida, Maryland, and New York were used to identify patients undergoing complex HPB surgery and to quantify hospital and surgeon procedure volumes. The effects of hospital and surgeon procedure volumes on casemix-adjusted inpatient mortality were analyzed using multilevel logistic regression models. RESULTS: For hepatic resection, hospital procedure volume predicted mortality (high versus low volume, odds ratio [OR] 0.48, p=0.04), but surgeon volume did not (p=0.42). For pancreatic resection, in contrast, both hospital (OR 0.32, p < 0.001) and surgeon (OR 0.30, p < 0.001) procedure volume predicted mortality. The hospital volume effect for pancreatic resection was largely explained by surgeon volume. In both procedure groups, volume-outcomes effects were very specific. Only volumes of the primary procedure were predictive of mortality; volumes of related HPB procedures and overall HPB volume demonstrated no independent effect on mortality. CONCLUSIONS: In HPB surgery, the relative contributions of hospital versus surgeon volume vary according to the specific procedure in question. In addition, the association between hospital or surgeon volume and in-hospital mortality is very specific to the procedure in question. High-volume expertise in one area of HPB surgery does not translate into improved outcomes for related procedures. These data may have implications for quality assessment and improvement, patient referral, and HPB surgical training. PMID- 19476787 TI - Utility of transjugular intrahepatic portosystemic shunts in liver-transplant recipients. AB - BACKGROUND: Transjugular intrahepatic portosystemic shunts (TIPS) have been used to control symptomatic portal hypertension in patients awaiting liver transplant. Although their role in pretransplantation patients is well established, their role in posttransplantation patients is unclear. STUDY DESIGN: Retrospective analyses were performed for 18 liver-transplant recipients who underwent TIPS for recurrent end-stage liver disease. Patients were evaluated in regard to gender, age, diagnoses, allograft type, indication for TIPS, portal pressures, laboratory results, Model for End-Stage Liver Disease (MELD) score, and outcomes. RESULTS: Median days from transplant to TIPS was 939 days (range, 122 to 3,415 days). Indications included variceal bleeding (n=2) and ascites (n=16). Ten patients (56%) responded to TIPS; TIPS prevented bleeding in both patients with varices, and it achieved symptomatic benefit in half of all patients with ascites. TIPS reduced median portal pressures from 22 mmHg (range, 17 to 50 mmHg) to 16 mmHg (range, 11 to 22 mmHg) and median portosystemic pressure gradients from 18 mmHg (range, 8 to 30 mmHg) to 8 mmHg (range, 2 to 12 mmHg). It increased median Model for End-Stage Liver Disease scores from 16 (range, 12 to 29) to 17 (range, 10 to 34) immediately and to 22 (range, 10 to 35) at 1 month. Six patients (33%) underwent retransplantation at a median of 58 days (range, 21 to 71 days) post TIPS. Of the remaining 12 patients, 3 (25%) were alive and well at a median of 90 days (range, 78 to 1,169 days) post-TIPS; 9 (75%) died at a median of 99 days (range, 13 to 1,400 days) post-TIPS. Subgroup analysis failed to demonstrate significant differences between patients whose ascites responded to TIPS (n=8) and patients whose ascites did not (n=8). Responders were younger, had higher baseline portal pressures, greater reductions in portal-systemic pressure gradients, and better hepatic function. CONCLUSIONS: Though small, this was the largest series to date of TIPS in liver-transplant recipients. Overall, 56% of patients responded to TIPS. No single factor predicted response or nonresponse of ascites to TIPS. Without retransplantation, 75% of patients died. Careful selection is necessary when considering TIPS for patients with ascites. PMID- 19476788 TI - Venous thromboembolism as a marker of quality of care in trauma. AB - BACKGROUND: Venous thromboembolism (VTE) is reported to occur among 7% to 58% of trauma patients. Variability in VTE rates might reflect differences in case mix and quality of care, but also screening practices or data capture. We explored the variation in VTE rates across trauma centers to determine its use as a measure of the quality of patient care. STUDY DESIGN: The National Trauma Data Bank (version 7.1, admission year 2006) was used to capture a cohort at risk for VTE. Crude and adjusted rates of VTE were determined, and the observed and expected rates were compared across centers. Outlier hospitals were defined as those with considerably more (or fewer) patients than expected. We then assessed the level of concordance between outlier status for deep vein thrombosis (DVT) and pulmonary embolism (PE). Intraclass correlation coefficients (ICC) were calculated to evaluate for the presence of a "center" effect using multilevel modeling. RESULTS: The 22,421 patients met inclusion criteria from 30 trauma centers. There was marked variability in the rate of VTE across centers, ranging from 0.2% to 13.3%, which was more pronounced for DVT (0.2% to 13.1%) than for PE (0% to 1.7%). There was poor concordance for DVT and PE outlier status. Intraclass correlation coefficient was four times greater for DVT (0.23) than for PE (0.06). CONCLUSIONS: There was substantial variation in rates of VTE across trauma centers. There was no relationship between DVT and PE outlier status, which is counter to the understanding of the biologic relationship between the two. Lastly, the very low Intraclass correlation coefficient for PE compared with DVT suggests that to a large extent, practice variation has very little impact on PE rates. In light of these findings and concerns about patient ascertainment of DVT, VTE rates might not be a useful measure of quality of care. PMID- 19476789 TI - Survival in lymph node negative adenocarcinoma of the esophagus after R0 resection with and without neoadjuvant therapy: evidence for downstaging of N status. AB - BACKGROUND: After esophagectomy, many patients who received neoadjuvant therapy have no evidence of lymph node involvement (N0 disease). Whether lymph nodes were initially involved and eradicated by the neoadjuvant therapy (down-staged) or if the nodes were never involved is a subject of debate. To address this issue, we compared clinical outcomes in N0 patients treated with neoadjuvant therapy with outcomes in patients treated with surgery alone. STUDY DESIGN: We reviewed records of 100 consecutive patients who underwent R0 esophagectomy for adenocarcinoma with pathologic N0 status. Seventy-five patients were treated by operation alone and 25 received neoadjuvant therapy. Tumor characteristics including length, depth, lymphovascular invasion, and degree of differentiation were compared and longterm survival was assessed by Kaplan-Meier analysis at a median of 46 months (interquartile range 26 to 77 months). RESULTS: Tumor characteristics were similar between groups. Recurrence was more common in patients who received neoadjuvant therapy compared with those treated with surgery alone (10 of 25 versus 10 of 75, p=0.0063). Patients with N0 disease after neoadjuvant therapy had a significantly worse survival than patients treated by surgery alone (49% versus 85%, p=0.005). CONCLUSIONS: Although neoadjuvant therapy may eradicate lymph node metastases, it does not result in the same outcomes as those achieved in patients with N0 disease treated with surgery alone. The poor clinical outcomes observed in N0 patients after neoadjuvant therapy suggest that they initially had node involvement and were downstaged by eradication of lymph node disease. PMID- 19476790 TI - Predictors of prosthetic graft infection after infrainguinal bypass. AB - BACKGROUND: Some patients require major leg amputation after lower-extremity prosthetic bypass for graft occlusion or failure of wound healing, despite a patent graft. Amputation above or below the knee was hypothesized to increase susceptibility to prosthetic graft infection in the ipsilateral extremity. STUDY DESIGN: All patients undergoing implantation of prosthetic infrainguinal arterial bypass grafts identified from a vascular surgical registry during a 12-year period were reviewed. Patient demographic data, comorbid conditions, and operative details were evaluated as risk factors, with graft infection among the primary outcomes of interest. RESULTS: Prosthetic graft infection occurred in 25 of 141 (18%) infrainguinal grafts and occurred most frequently after major amputation (41% versus 6%; odds ratio [OR] = 12; 95% CI, 4.1 to 34) or early reoperation after initial grafting (70% versus 16%; OR = 11; 95% CI, 1.9 to 63). Risk was highest after amputation within 4 weeks of bypass (70% versus 32%; OR = 5.0; 95% CI, 1.1 to 23). Graft thrombosis (84% versus 39%; OR = 8.3; 95% CI, 2.7 to 26) and presence of gangrene (52% versus 23%; OR = 3.6; 95% CI, 1.5 to 8.7) also increased infection risk. Independent predictors for development of graft infection were identified by stepwise regression analysis to be amputation (p < 0.001), early reoperation (p = 0.002), and absence of renal failure (p = 0.038) but not gangrene (p = 0.090). Amputations performed within 6 months of the initial bypass operation were more likely to be associated with prosthetic graft infection than those performed later than 6 months (52% versus 17%; OR = 5.3; 95% CI, 1.3 to 22). CONCLUSIONS: Amputation increases risk of prosthetic graft infection, especially when performed early or after failed revascularization. Consideration should be given to partial or complete removal of a prosthetic graft above the level of the amputation under these conditions. PMID- 19476791 TI - Association of kyphosis and spinal skeletal abnormalities with intrathoracic stomach: a link toward understanding its pathogenesis. AB - BACKGROUND: Modern-day concepts about the pathogenesis of an intrathoracic stomach include crural diaphragm muscular deterioration, loss of phrenoesophageal ligament integrity, and presence of abdominothoracic pressure gradients. The role of spinal abnormalities has received little attention. Based on clinical observation, we hypothesized that kyphosis and other spinal diseases are components of the pathophysiology of an intrathoracic stomach. STUDY DESIGN: The study population consisted of 98 patients (men, n = 22; women, n = 76; mean age 69.4 years) undergoing operations for type III or IV hiatal hernia with an intrathoracic stomach. Twenty-four age- and gender-matched control patients without hiatal hernia undergoing pulmonary or pleural procedures were used for comparison. Chest radiographs were assessed for spinal abnormalities, including degree of kyphosis, measured from superior T4 to inferior T12 (modified Cobb method), spinal fractures, osteoporosis, and scoliosis. Statistical analyses included two-sample t-test and Fisher's exact test. RESULTS: Patients with intrathoracic stomach had a greater degree of kyphosis than control patients (Cobb angle, 50.2 degrees versus 39.7 degrees; p < 0.001). This difference was most pronounced in women (Cobb angle, 51.7 degrees versus 40.4 degrees; p < 0.001), although the difference in men was not significant (Cobb angle, 45.0 degrees versus 38.1 degrees; p = 0.25). Patients with an intrathoracic stomach had significantly more vertebral fractures (37 of 98 [38%] versus 3 of 24 [13%]; p < 0.05). There was no difference in prevalence of degenerative changes (51 of 98 [52%], versus 13 of 24 [54%]), osteopenia (30 of 98 [31%] versus 6 of 24 [25%]), and scoliosis (27 of 98 [28%] versus 6 of 24 [25%]). CONCLUSION: Patients with an intrathoracic stomach have a higher degree of kyphosis and more vertebral fractures than age- and gender-matched controls. These data suggest that change in spinal curvature can be important in the pathogenesis of the intrathoracic stomach, a growing problem of our aging population. PMID- 19476792 TI - Polypoid lesions of the gallbladder: diagnosis and followup. AB - BACKGROUND: Polypoid lesions of the gallbladder (PLG) are commonly seen on ultrasonography (US), but optimal management of this problem is ill-defined. The aims of this study were to assess the natural history and the histologic characteristics of US-detected PLG. STUDY DESIGN: Patients with PLG detected by abdominal US were identified retrospectively. Patients with infiltrative masses suspicious for gallbladder cancer were not included. Histologic findings were analyzed in patients who underwent cholecystectomy, and change in polyp size was determined in patients who underwent serial US imaging. RESULTS: From 1996 through 2007, 417 patients with PLG detected on US were identified. Two hundred twenty-nine patients (55%) were women, and median age was 59 years (range 20 to 94 years). Two hundred sixty-five patients (64%) were found to have PLG on US during the workup of other unrelated disease; 94 patients (23%) had abdominal symptoms. Ninety-four percent of patients had PLG< or =10 mm, and 7% had PLG>10 mm; 59% of patients had a single polyp and 12% had gallstones. Among 143 patients who had repeat US followup, growth was observed in only 8 patients (6%). Cholecystectomy (n=80) revealed that most patients had either pseudopolyps (58%) or no polyp (32%). Neoplastic polyps (adenoma) were found in 10% of patients. In situ cancer was seen in one patient with a 14-mm lesion. CONCLUSIONS: Small PLG (< or =10 mm in diameter) detected by US are infrequently associated with symptoms and can be safely observed. The risk of invasive cancer is very low, and was not seen in any patient in this study. PMID- 19476793 TI - Comparing the quality of the suture anastomosis and the learning curves associated with performing open, freehand, and robotic-assisted laparoscopic pyeloplasty in a swine animal model. AB - BACKGROUND: It is believed that robotic assistance allows for improved suture reapproximation of tissue and decreases the lengthy learning time that is needed to master laparoscopic suturing. But there have been no studies directly comparing the efficiency of robotic-assisted laparoscopic surgery (RALS) to freehand laparoscopy (LS) and open surgery (OS). The purpose of this study was to compare the quality of the suture anastomosis of the ureteropelvic junction (UPJ) using the three techniques and to evaluate their associated learning curves. STUDY DESIGN: The operative time for dismembered pyeloplasties performed in 57 pigs by 3 inexperienced and 1 experienced surgeon using each of the techniques was measured. The anastomosis was evaluated for water tightness and patency using antegrade and retrograde urodynamic measurements immediately after surgery and 2 weeks postoperatively. The histology of the operated UPJ was also evaluated at 15 days postoperatively. RESULTS: RALS had a shorter procedural time and less steep learning curve compared with LS. Urodynamic measurements for patency and water tightness of the UPJ were comparable to those in the OS group. But with experience, both the RALS and LS procedural times and the urodynamic measurements for water tightness and patency of the UPJ approached those of the OS group. Histologic evaluation demonstrated that there was less collagen III deposition around the operated UPJ in pigs that underwent RALS compared with LS and OS. CONCLUSIONS: Among inexperienced surgeons, the efficiency of performing suturing using RALS is operator independent, requires less time to learn, and is better than those done by LS technique. PMID- 19476794 TI - The present and future use of physician extenders in general surgery training programs: one response to the 80-hour work week. AB - BACKGROUND: The aim of this study was to assess the use of physician extenders (PEs) in general surgery residency programs. STUDY DESIGN: We surveyed the program directors in surgery for the number of chief residents, PEs on general surgery services, PE duties, whether PEs were hired in response to Accreditation Council for Graduate Medical Education work-hour restrictions, plans to hire additional PEs, and program type. Data were analyzed using the Student's t-test; p values are two-tailed and considered significant if <0.05. RESULTS: There were 163 programs (65%) that responded, (87 university, 70 nonuniversity, and 6 military programs), with a total of 689 graduating chief residents per year. One hundred sixty programs use 840 PEs (median, 3.5 PEs per program; mean, 5.3 PEs per program, 2 PEs per chief resident). One hundred twenty-seven programs (79%) use at least 1 PE (range 1 to 50 PEs); 93 programs (57%) hired 513 (61%) PEs in response to work-hour restrictions. Before 2003, the mean number of PEs per program was 2.0; after 2003, there were 5.3 per program (p=0.0001). Most common uses of PEs included taking histories and physicals (84%), seeing consults (58%), first-assisting (52%), and seeing patients in the emergency department (47%). Forty-seven of 162 (29%) programs plan to hire more PEs in the next 3 years, 76 programs (47%) would like to, but are unsure of funding; 23 programs (14%) are not planning to increase the total, and 16 programs (10%) are unsure. With available funding, 431 additional PEs may be hired in the next 3 years, for a total of 1,271 PEs in 163 programs, or an average of 7.8 PEs per program and 1.8 PEs per chief resident. CONCLUSIONS: PEs have been hired in large numbers to assist on general surgery teaching services, with most hired in response to Accreditation Council for Graduate Medical Education work-hour restrictions, and most of their duties are intended to aid resident education. Almost 80% of programs currently use PEs; 76% would like to hire more. Currently 1.2 PEs are used per graduating chief resident; this could increase to 1.8 PEs per chief resident in the next 3 years. PMID- 19476795 TI - Hemoglobin-based oxygen carrier induces heme oxygenase-1 in the heart and lung but not brain. AB - BACKGROUND: The clinical sequel of ischemia and reperfusion remains a challenge in several clinical areas. Overexpression of heme oxygenase-1 (HO-1), using viral vectors, endotoxemia, and hypoxia, provides protection against ischemia and reperfusion injury. To date, however, no clinically viable therapy exists to safely induce HO-1. We have recently observed that administration of a hemoglobin based oxygen carrier (HBOC) attenuates postinjury systemic inflammation. We have further demonstrated that an HBOC can induce HO-1 in vitro. We now explore the tissue-specific induction of heme oxygenase-1 after administration of an HBOC. STUDY DESIGN: Rats were infused with doses of HBOC or saline through femoral vein injection (n=5 per group). Animals were sacrificed and organs were flushed. Heart, lung, and brain samples were taken for evaluation of total organ levels of HO-1 induction and for histologic localization of the cellular expression of the HO-1. Heat shock protein 72 levels were also analyzed to determine whether HO-1 induction was a generalized stress response. RESULTS: Both the heart and lung demonstrated a dose-dependent induction of total organ HO-1. Interestingly, brain tissue did not have any significant amount of HO-1, either at baseline or after HBOC therapy. The cellular localization of HO-1 between organs was also specific, predominantly occurring in the cardiac myocyte and alveolar macrophages. Heat shock protein 72 levels were not significantly changed in any group examined, suggesting the induction of HO-1 is specific. CONCLUSIONS: This study demonstrates that a clinically accessible product, HBOC, can specifically and selectively induce the expression of the protective enzyme HO-1 in vivo. These findings begin to characterize which organ systems may benefit by preischemic treatments with HBOC and further expand potential clinical applications of HBOCs. PMID- 19476796 TI - A national analysis of the relationship between hospital volume, academic center status, and surgical outcomes for abdominal hysterectomy done for leiomyoma. AB - BACKGROUND: Volume-to-outcomes relationships have been established for high-risk surgical procedures. To determine whether hospital volume and academic center status affect surgical outcomes in a lower-risk procedure, morbidity and mortality in patients undergoing abdominal hysterectomy for leiomyoma were evaluated. STUDY DESIGN: Administrative data from the National Inpatient Sample were used to conduct a retrospective analysis of 172,344 individuals who had primary diagnoses of leiomyomata (ICD-9 diagnosis codes of 218.x in the first 2 positions) and who underwent abdominal hysterectomy (ICD-9 procedure codes 68.4 in the first 2 positions) from 1999 to 2003. Comparison was made between teaching hospitals versus nonteaching hospitals and annual case volume in quintiles. Morbidity was considered to be any postoperative condition that is not an expected outcome of hysterectomy and defined as instances in which a patient suffered hemorrhage, ureteral injury, bladder injury, intestinal injury, wound dehiscence, wound infection, deep vein thrombosis, pulmonary embolism, or required blood transfusion. RESULTS: A total of 37 deaths were observed. Mortality was not significantly related to hospital volume or academic medical center status. In contrast, morbidity was found to have a positive association with academic medical center status (odds ratio = 1.34; 95% CI, 1.23 to 1.45), although an inverse relationship between volume and morbidity was observed for extended length of stay (> 3 days) and blood transfusion outcomes in the first 3 (lowest) volume quintiles and for pulmonary embolism in the highest-volume quintile. No important association with volume was found for hemorrhage, ureteral injury, bladder injury, or intestinal injury. CONCLUSIONS: Unlike high-risk procedures, such as esophagectomy, pediatric cardiac surgery, and pancreaticoduodenectomy, mortality for abdominal hysterectomy done for benign indication does not improve with hospital volume or academic center status. The statistically significant positive association between academic medical center status and morbidity merits additional characterization to target areas for improvement. PMID- 19476798 TI - Quality improvement in the surgical approach to advanced ovarian cancer: the Mayo Clinic experience. AB - BACKGROUND: After observing disparate rates of cytoreduction, we initiated efforts to improve outcomes through feedback and education, and we reassessed outcomes. STUDY DESIGN: Outcomes from group A (2006 and 2007, n=105) were compared with those from the cohort predating quality-improvement efforts (group B, 2000 to 2003, n=132). All stage IIIC ovarian cancer patients at our institution were evaluated for tumor dissemination, age, performance status, surgical complexity, residual disease (RD), morbidity, and mortality. A surgical complexity score previously described was used to categorize extent of operation. RESULTS: No significant differences in age, performance status, or extent of disease were observed between cohorts. Surgical complexity increased after initiation of quality improvement (mean surgical complexity score, 5.5 to 7.1; p < 0.001), rates of optimal RD (< 1 cm) improved from 77% to 85% (p=0.157), and rates of complete resection of all gross disease rose from 31% to 43% (p=0.188). In the subset of patients with carcinomatosis most likely to benefit from extended surgical resection, radical procedures were used more frequently (63% versus 79%; p=0.028), rates of optimal debulking (RD<1 cm) increased (64% to 79%), and the rate of RD=0 increased from 6% to 24% (p=0.006). When disease was noted on the diaphragm, procedures to remove the disease were more frequently used (38% to 64%; p=0.001). The rates of major perioperative morbidity (group B, 21% versus group A, 20%; p=0.819) and 3-month mortality (8% versus 6%; p=0.475) were not affected despite this more aggressive surgical approach. CONCLUSIONS: Analysis of outcomes with appropriate feedback and education is a powerful tool for quality improvement. We observed improvements in rates of cytoreduction and use of specific radical procedures, with no increase in morbidity as a result of this process. PMID- 19476797 TI - Myocardial survival signaling in response to stem cell transplantation. AB - BACKGROUND: Experimental human stem cell transplantation to the heart has begun, but the mechanisms underlying benefits seen in preclinical models, both at the site of cell injection and at more distant regions, remain uncertain. We hypothesize that these benefits can be best understood first at the level of key intracellular signaling cascades in the host myocardium, which can be responsible for functional and structural preservation of the heart. STUDY DESIGN: Western blot and ELISA were used to assess key pathways that regulate cardiac myocyte survival and hypertrophy in both the infarct/borderzone and remote myocardium of C57/B6 mouse hearts subjected to coronary artery ligation, with subsequent injection of either vehicle or bone marrow-derived adult mesenchymal stem cells (MSC). RESULTS: Improved left ventricular function with MSC transplantation was associated with a relative preservation of Akt phosphorylation (activation) and of phosphorylation of downstream mediators of cell survival and hypertrophy. There was no substantial difference in activation of mitogen-activated protein kinase p38, and activation of the antiapoptotic mitogen-activated protein kinase extracellular signal-regulated kinase was lower at 1 week after MSC treatment, but rose beyond controls by week 2. Similar changes were observed in both the infarct/borderzone and the remote myocardium. CONCLUSION: Stem cell transplantation in the post-MI murine myocardium is associated with preservation of Akt signaling. Together with a possible later increase in extracellular signal regulated kinase activation, this signaling change might be responsible for cardioprotection. Additional focused investigation might identify elements in transplantation regimens that optimize this mechanism of benefit, and that can increase the likelihood of human clinical success. PMID- 19476799 TI - Improving quality improvement: a methodologic framework for evaluating effectiveness of surgical quality improvement. PMID- 19476800 TI - Informed consent and the surgeon. PMID- 19476801 TI - Interpreting study designs in surgical research: a practical guide for surgeons and surgical residents. PMID- 19476802 TI - Segond fracture. PMID- 19476803 TI - Polyorchia secondary to transverse division of the embryonic genital ridge and ipsilateral mesonephric duct. PMID- 19476804 TI - Who should be outraged? PMID- 19476805 TI - "Ghost" publications among applicants to a general surgery residency program. PMID- 19476810 TI - Surgical education: foundations and values. PMID- 19476811 TI - Genetic variation in the autonomic nervous system affects mortality: a study of 1,095 trauma patients. AB - BACKGROUND: We have previously demonstrated an unappreciated link between the autonomic nervous system and mortality, heart rate variability, and physiologic complexity. STUDY DESIGN: Genetic variation in adrenergic receptors or key enzymes in catecholamine degradation could be associated with, and potentially explain, autonomic nervous system dysfunction and its impact on mortality after severe trauma. Three genetic polymorphisms critical to the adrenergic pathway were evaluated: beta-2 adrenergic receptor (ADBR2: Q27E), alpha-1a adrenergic receptor (ADRA1A:R347C), and catechol-O-methyl transferase (COMT: V158M). The study population consisted of 1,095 trauma admissions between April 2005 and April 2007. These patients all had genotyping performed using mass spectrometric analysis (Sequenom, Inc). The genetic data were linked with detailed demographic and clinical data. Trauma Related Injury Severity Score (TRISS) probability of survival was used as a composite measure of injury severity, admission physiology, and demographic factors in the multivariate logistic regression analyses of mortality outcomes data. RESULTS: The overall mortality rate for the study population was 14.2% (155 of 1,095). Univariate comparisons of genotypes with mortality revealed a significant association with the ADBR2 polymorphism: CC=15.9%, GC=14.8% and GG=7.6%, p=0.02. The apparently protective ADBR2 GG genotype was seen in 15.5% (170 of 1,095) of the study population. In multivariate analysis, which included adjustment for TRISS, the ADBR2 GG genotype was associated with reduced mortality (odds ratio 0.36, p=0.002). CONCLUSIONS: Genetic variation in the beta-2 adrenergic receptor (ADBR2:Q27E) associated with bronchial constriction appears protective (odds ratio 0.36), perhaps by making the receptor resistant to downregulation. These genetic data support the emerging understanding of critical role of the autonomic nervous system in the response to injury. PMID- 19476813 TI - Effective triage can ameliorate the deleterious effects of delayed transfer of trauma patients from the emergency department to the ICU. AB - BACKGROUND: Emergency department (ED) crowding and delays in care represent a national problem; no large study has examined the impact of such delays in surgical patients. We sought to determine the impact of delayed transfer from the ED on outcomes in trauma/emergency general surgical patients in a center that has developed a policy to triage more critically ill/severely injured patients to earlier ICU admission. STUDY DESIGN: All trauma patients admitted from January 2005 to April 2007 in a Level I trauma center were divided into a nondelayed (6 hours) group. Factors associated with their injuries and outcomes were determined from a large prospective database and all deaths were examined by root-cause analysis. Sentinel events were examined in all deaths and among randomly selected survivors. RESULTS: Among 3,918 patients, ED stay was often prolonged. The nondelayed group spent a mean of 3 hours in the ED compared with 14.6 hours in the delayed group. Patients admitted earlier were more seriously injured and had markedly worse outcomes, with overall mortality of 18% versus 2.3% in the nondelayed and delayed group, respectively. Mortality did not increase with time spent in the ED but, in fact, decreased after 4 hours. Case analysis disclosed two deaths that might have been altered by earlier ICU transfer. CONCLUSION: Experienced clinicians can effectively triage more critically injured patients to earlier ICU admission and alter associations between ED length of stay and mortality. Hospitals with a large trauma/emergency general surgery caseload resulting in delays in ED throughput should institute policies and procedures for triage of more severely injured patients for early ICU admission and develop a monitoring system to ensure that delays do not adversely affect patient outcomes. PMID- 19476817 TI - Effects of increased vascular surgical specialization on general surgery trainees, practicing surgeons, and the provision of vascular surgical care. AB - BACKGROUND: Vascular surgical education for general surgery residents is concerning as endovascular interventions increase and vascular surgery expands. The purpose of this study was to examine the effects these factors have on vascular surgery case numbers for general surgery residents and statewide surgeons and to report on former general surgery residents' perceptions of vascular surgery in training and practice. STUDY DESIGN: Case numbers for all general surgery residents graduating from the Greenville Hospital System from 1991 to 2007 and for the vascular surgery fellows graduating from 2003 to 2007 were obtained. A database identified case numbers and physician specialty for vascular procedures from 1997 through 2006. A survey gained perspectives of graduated general surgery residents on the vascular experience during residency and practice and on postresidency vascular caseload. RESULTS: There was significant decline in resident participation in open abdominal aortic aneurysm (22.4 versus 7.7), carotid endarterectomy (37.2 versus 31.1), aortobifemoral bypass (18.6 versus 5.5), and lower extremity bypass (42.8 versus 19.1). Numbers for dialysis access creation (49.0 versus 57.1) were maintained. Statewide, comparing 1997 with 2006, the percentages of procedures performed by vascular surgeons were: abdominal aortic aneurysm (29.3% versus 49%; p < 0.001), carotid endarterectomy (28.9% versus 45.5%; p < 0.001), and dialysis access (4.6% versus 12.3%; p=0.020). The survey of general surgery graduates revealed lower extremity bypass, carotid endarterectomy, abdominal aortic aneurysm, and dialysis access are important in training. Dialysis access was the most common operation performed by the general surgery graduates. CONCLUSIONS: There is a trend toward vascular surgeons and vascular residents performing most open vascular cases. Currently practicing surgeons believe there is value to vascular exposure for general surgeons in training, and vascular surgery should remain in general surgery training. PMID- 19476815 TI - Longterm outcomes for whole and segmental liver grafts in adult and pediatric liver transplant recipients: a 10-year comparative analysis of 2,988 cases. AB - BACKGROUND: Data on longterm outcomes after liver transplantation with partial grafts are limited. We compared 10-year outcomes for liver transplant patients who received whole grafts (WLT), split grafts from deceased donors (SLT), and partial grafts from living donors (LDLT). STUDY DESIGN: We conducted a single center analysis of 2,988 liver transplantations performed between August 1993 and May 2006 with median followup of 5 years. Graft types included 2,717 whole-liver, 181 split-liver, and 90 living-donor partial livers. Split-liver grafts included 109 left lateral and 72 extended right partial livers. Living-donor grafts included 49 left lateral and 41 right partial livers. RESULTS: The 10-year patient survivals for WLT, SLT, and LDLT were 72%, 69%, and 83%, respectively (p=0.11), and those for graft survival were 62%, 55%, and 65%, respectively (p=0.088). There were differences in outcomes between adults and children when compared separately by graft types. In adults, 10-year patient survival was significantly lower for split extended right liver graft compared with adult whole liver and living-donor right liver graft (57% versus 72% versus 75%, respectively, p=0.03). Graft survival for adults was similar for all graft types. Retransplantation, recipient age older than 60 years, donor age older than 45 years, split extended right liver graft, and cold ischemia time>10 hours were predictors of diminished patient survival outcomes. In children, the 10-year patient and graft survivals were similar for all graft types. CONCLUSIONS: Longterm graft survival rates in both adults and children for segmental grafts from deceased and living donors are comparable with those in whole organ liver transplantation. In adults, patient survival was lower for split compared with whole grafts when used in retransplantations and in critically ill recipients. Split graft-to-recipient matching is crucial for optimal organ allocation and best use of a scarce and precious resource. PMID- 19476819 TI - Impact of a monitored program of care on incidence of ventilator-associated pneumonia: results of a longterm performance-improvement project. AB - BACKGROUND: Ventilator-associated pneumonia (VAP) remains a major source of morbidity, mortality, and expense in the ICU despite therapies directed against it. STUDY DESIGN: A retrospective review of a prospectively developed performance improvement project monitoring the incidence of VAP in two adjacent ICUs was conducted. In response to an excessive VAP rate, weekly multidisciplinary team meetings were instituted to review data, develop care protocols, and modify care routines. Protocol compliance was monitored daily and feedback provided weekly to the care teams. VAP rates were determined by the institutional Infection Control Committee and reviewed monthly with the ICU multidisciplinary team. Duration of the investigational period was 10 years. RESULTS: A standardized ventilator weaning protocol was instituted with confirmed 95% use. Additional modifications of care, such as patient positioning, use of specific endotracheal tubes to minimize aspiration of supraglottic secretions, an oral-care regimen, and aggressive antibiotic stewardship were standardized, with a compliance rate >90%. VAP rates dropped from 12.8 per 1,000 patient-days in 1998 to 1.1 in 2007 in the burn trauma ICU and from 21.2 to <1 in the neurotrauma ICU in the same time frame. Also, mean ventilator length of stay decreased from 6 days to 4.2 and from 5.8 days to 4.75 simultaneously in the respective ICUs. Such performance improvement has been sustained since implementation of the program. CONCLUSION: A systematic, monitored program of standardized care protocols can markedly reduce VAP rate in the ICU. PMID- 19476821 TI - A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. AB - BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive approach for treating in-transit extremity melanoma, with only two US single-center studies reported. Establishing response and toxicity to ILI as compared with hyperthermic isolated limb perfusion is important for optimizing future regional chemotherapeutic strategies in melanoma. STUDY DESIGN: Patient characteristics and procedural variables were collected retrospectively from 162 ILIs performed at 8 institutions (2001 to 2008) and compared using chi-square and Student's t test. ILIs were performed for 30 minutes in patients with in-transit melanoma. Melphalan dose was corrected for ideal body weight (IBW) in 42% (n = 68) of procedures. Response was determined at 3 months by Response Evaluation Criteria in Solid Tumors; toxicity was assessed using the Wieberdink Limb Toxicity Scale. RESULTS: In 128 evaluable patients, complete response rate was 31%, partial response rate was 33%, and there was no response in 36% of patients. For all patients (n = 162), 36% had Wieberdink toxicity grade >or=3 with one toxicity related amputation. On multivariate analysis, smaller limb volumes were associated with better overall response (p = 0.021). Use of papaverine in the circuit to achieve cutaneous vasodilation was associated with better response (p < 0.001) but higher risk of grade >or=3 toxicity (p = 0.001). Correction of melphalan dose for ideal body weight did not alter complete response (p = 0.345), but did lead to marked reduction in toxicity (p < 0.001). CONCLUSIONS: In the first multi-institutional analysis of ILI, a complete response rate of 31% was achieved with acceptable toxicity demonstrating this procedure to be a reasonable alternative to hyperthermic isolated limb perfusion in the management of advanced extremity melanoma. PMID- 19476823 TI - Reoperative surgery in sporadic Zollinger-Ellison Syndrome: longterm results. AB - BACKGROUND: Most patients with Zollinger-Ellison Syndrome (ZES), even those in whom gastrinoma is found and resected at initial operation, will suffer from persistent or recurrent disease in longterm followup. There is currently no consensus about managing patients with recurrent or persistent ZES. Our unit has historically maintained an aggressive approach toward monitoring and reoperation for patients with sporadic ZES. STUDY DESIGN: We performed a review of a consecutive series of patients evaluated and managed at our institution between 1970 and 2007 for ZES. "Biochemical cure" was defined as normal serum gastrin assays and negative imaging studies. Reoperations were performed for elevations in serum gastrin assays and positive findings on imaging studies. RESULTS: Fifty two patients with sporadic ZES were analyzed. Median followup was 14 years. Among patients with sporadic ZES, 37 patients underwent operative management. The most common operations were resection of duodenal gastrinoma (n=8) and total gastrectomy (n=7). Nine patients underwent 15 reoperations for recurrent or persistent disease. "Biochemical cure" was obtained in four patients (44%) undergoing reoperation for ZES. Three of these patients remained without evidence of recurrence at 4, 9, and 12 years after their curative re-resection. Only one of nine patients who underwent reoperation died of metastatic gastrinoma. CONCLUSIONS: Primary and reoperative surgery in patients with sporadic ZES results in a significant rate of "biochemical cure." In selected patients with recurrent or persistent disease, reoperation for resection of gastrinoma is associated with excellent longterm survival and is warranted. PMID- 19476825 TI - Less is more: improved outcomes in surgical patients with conservative fluid administration and central venous catheter monitoring. AB - BACKGROUND: The ARDS Clinical Trials Network Fluid and Catheter Treatment Trial (FACTT) addressed fluid management and central monitoring of patients with acute respiratory distress syndrome/acute lung injury (ARDS/ALI). Because surgical patients may have been fundamentally different from the overall FACTT cohort, we set out to separately analyze the surgery patients in the trial. STUDY DESIGN: We performed a posthoc, surgical subgroup analysis of 1,000 patients enrolled in the FACTT. Patients were randomized using a 2x2 factorial design comparing a conservative (CON) versus a liberal (LIB) strategy of fluid management and the use of a pulmonary artery catheter (PAC) or a central venous catheter (CVC). The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days, ICU-free days, and dialysis-free days until hospital discharge up to day 90. We defined surgical patients as those admitted to a surgical ICU, burn ICU, or cardiac surgical ICU; trauma patients; or those with an APACHE III surgical admission type. RESULTS: There were 244 surgical patients. Risk of death within 60 days of randomization did not vary with catheter or fluid management, and a corresponding lack of effect was evident with regard to dialysis-free days. Ventilator-free days were increased in the fluid-conservative group (LIB, 13+/-1 days; CON, 15+/-1 days; p=0.04) at 28 days. CVC patients had more ventilator-free days at 28 and 90 days (28 days: CVC, 16+/-1 days; PAC, 13+/ 1 days; p=0.03; 90 days: CVC, 64+/-3 days; PAC, 57+/-4 days; p=0.03). CVC patients had more ICU-free days at 90 days (90 days: CVC, 63+/-3 days; PAC, 55+/ 3 days; p=0.04). CONCLUSIONS: The risk of death did not vary with fluid management or catheter. A conservative fluid-administration strategy and central venous catheter monitoring resulted in more ventilator-free and ICU-free days in surgical patients with acute lung injury, and conservative fluid administration did not result in more renal failure. PMID- 19476827 TI - Does type of pancreaticojejunostomy after pancreaticoduodenectomy decrease rate of pancreatic fistula? A randomized, prospective, dual-institution trial. AB - BACKGROUND: Pancreatic fistula (PF) is one of the most common complications after pancreaticoduodenectomy. There have been no large prospective randomized trials evaluating PF rates comparing invagination versus duct to mucosa pancreaticojejunostomy. We tested the hypothesis that a duct to mucosa pancreaticojejunostomy would reduce the PF rate. STUDY DESIGN: Between August 2006 and May 2008, 197 patients at two institutions underwent pancreaticoduodenectomy by a total of 8 experienced pancreatic surgeons as part of this prospective randomized trial (clinical trial no. NCT00359320). All patients were stratified by pancreatic texture and randomized to either an invagination or a duct to mucosa pancreaticojejunal anastomosis. Recorded variables included pancreatic duct diameter, operative time, blood loss, complications, and pathology. Primary end point was PF rate, as defined by the International Study Group on Pancreatic Fistula. Secondary end points included PF grade, postoperative length of hospital stay, other morbidities, and mortality. RESULTS: Rate of PF for the entire cohort was 17.8%. There were 23 fistulas (24%) in the duct to mucosa cohort and 12 fistulas (12%) in the invagination cohort (p < 0.05). The greatest risk factor for a PF was pancreas texture: PF developed in only 8 patients (8%) with hard glands, and in 27 patients (27%) with a soft gland. There were two perioperative deaths (both in the duct to mucosa group), with the proximate causes of death being PF, followed by bleeding and sepsis. CONCLUSIONS: This dual-institution prospective randomized trial reveals considerably fewer fistulas with invagination compared with duct to mucosa pancreaticojejunostomy after pancreaticoduodenectomy. Results confirm increased PF rates in soft as compared with hard glands. Additional studies are needed to define the optimal technique of pancreatic reconstruction after pancreaticoduodenectomy. PMID- 19476829 TI - Trauma surgeon mortality rates correlate with surgeon time at institution. AB - BACKGROUND: Trauma centers have been created to bring traumatized patients together with experienced surgeons. We reviewed our outcomes to determine if mortality rates for high Injury Severity Scores (>or= 35) correlate with surgeon experience at our trauma center. STUDY DESIGN: Using our prospectively collected database, we compared our results with mean mortality for high-volume American College of Surgeon-certified trauma centers reporting to the National Trauma Data Bank. Mortality rates for our 11 trauma surgeons were correlated with years of experience as faculty surgeons at our institution during a 2-year period. Statistical analysis was done with chi-square or weighted linear regression; significance was defined as p < 0.05. RESULTS: Our trauma center mortality rates were significantly below the mean rates of National Trauma Data Bank at all levels of injury (chi-square, p < 0.05). Despite this success, there was a significant correlation between years of experience as a surgeon at our institution and improved outcomes for patients with an Injury Severity Score >or= 35 (weighted linear regression, p < 0.05). It took, on average, 7.9 years of experience at our trauma center to reach benchmark mortality rates. CONCLUSIONS: Mortality rates for severely injured patients correlate significantly with surgeon experience at our institution. The training process does not end with fellowship or surgical residency, and surgeons new to an institution should be closely monitored and mentored to minimize mortality rates of severely injured patients. Even at a very high volume trauma center with overall results substantially better than mean expected survival, we can demonstrate that experience makes a difference. PMID- 19476831 TI - INTERMACS: interval analysis of registry data. AB - BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is an NIH-sponsored registry of US FDA-approved mechanical circulatory support devices (MCSDs) used for destination therapy, bridge to transplantation (BTT), or recovery of the heart. INTERMACS data were analyzed through the most recent quarter ending March 31, 2008. STUDY DESIGN: INTERMACS variables include demographics, patient outcomes (survival and adverse events), hemodynamic data, and laboratory values. Data were analyzed with competing outcomes methods. Risk factors were identified for death and transplantation. RESULTS: Ninety-four sites have prospectively enrolled 483 patients in INTERMACS (BTT, 80%; destination therapy, 15%; bridge to recovery, 5%). Forty-two percent of patients had critical cardiogenic shock before implantation, 38% had progressive circulatory decline despite inotropic agents, and 8% were stable but inotropic agent-dependent. The remaining 12% had recurrent advanced heart failure, severe exercise intolerance, or advanced class III heart failure. At 6 months postimplantation, the competing outcomes for the 483 patients included ongoing support (42%), cardiac transplantation (33%), cardiac recovery with pump removal (3%), or death (22%). The most common causes of death were central nervous system events (11%), cardiovascular failure (8%), or respiratory failure (8%). Less common causes were infection (4%), device malfunction (4%), and liver failure (3%). Survival for BTT and destination therapy were similar (p = 0.53). Patient profile at the time of implantation (critical cardiogenic shock versus others) influenced survival (p = 0.007), as did device configuration (left ventricular assist device versus biventricular ventricular assist device; p < 0.0001). CONCLUSIONS: INTERMACS has increasing participation among domestic MCSD centers. The influence of preimplantation patient condition on survival underscores the importance of timely referral before critical cardiogenic shock occurs. As more devices achieve US FDA approval, INTERMACS will become useful for comparing MCSDs. PMID- 19476833 TI - Closed loop control of inspired oxygen concentration in trauma patients. AB - BACKGROUND: Transport of mechanically ventilated patients in a combat zone presents challenges, including conservation of resources. In the battlefield setting, provision of oxygen supplies remains an important issue. Autonomous control of oxygen concentration can allow a reduction in oxygen usage and reduced mission weight. METHODS: Trauma patients requiring ventilation and inspired oxygen concentration (FIO(2)) > 0.40 were evaluated for study. Patients were randomized to consecutive 4-hour periods of closed loop control or standard care. The system for autonomous control consisted of a ventilator, oximeter, and a portable computer. The computer housed the control algorithm and collected data every 5 seconds. The controller goal was to maintain pulse oximetry (SpO(2)) at 94 +/- 2% through discrete changes of 1% to 5% every 30 seconds. Ventilator settings and SpO(2) were recorded every 5 seconds for analysis. RESULTS: Forty five patients were enrolled in this study. Oxygen saturation was maintained in the 92% to 96% saturation range 33 +/- 36% of the time during clinician control versus 83 +/- 21% during closed loop control. Time spent at the target SpO(2) 92% to 96% was 193.3 +/- 59.18 minutes during closed loop control and 87.08 +/- 87.95 minutes during clinician control (p < 0.001). Hyperoxemia was more frequent during clinician control (144.29 +/- 90.09 minutes) than during closed loop control (38.91 +/- 55.86 minutes; p < 0.001). There were no differences in the number of episodes of SpO(2) < 88%. Oxygen usage was reduced by 32% during closed loop control. CONCLUSION: Closed loop control of FIO(2) offers the opportunity for maximizing oxygen resources, reducing mission weight, and providing targeted normoxemia without increasing risk of hypoxemia in ventilated trauma patients. PMID- 19476835 TI - Comparison of interventional outcomes according to preoperative indication: a single center analysis of 2,240 limb revascularizations. AB - BACKGROUND: Outcomes after lower extremity revascularization are usually reported according to the level of peripheral arterial disease (PAD, aortoiliac or infrainguinal) or the method of treatment (open or endovascular surgery). Outcomes stratified by indication, ie, claudication or critical limb ischemia (rest pain and tissue loss), have not been well studied. The purpose of this study was to compare postoperative outcomes according to the preoperative indications. STUDY DESIGN: Outcomes of 2,240 consecutive limb revascularizations in 1,732 patients from January 1998 through December 2005 were stratified and examined according to preoperative indication: claudication (n=999 limbs), ischemic rest pain (n=464 limbs), or tissue loss (n=777 limbs). End points measured included primary and secondary interventional or operative patency, limb salvage, survival, amputation-free survival, maintenance of ambulation, maintenance of independence, and resolution of presenting symptoms. RESULTS: The proportion of medical comorbidities and the severity of disease increased significantly by cohort from claudication to rest pain to tissue loss. With a mean followup of 1,089 days (range 0 to 3,689 days), overall outcomes performance declined consistently according to indication for all end points measured at 5 years (claudication, rest pain, tissue loss, p value): secondary reconstruction patency (93%, 80%, 66%, respectively; p < 0.001), limb salvage (99%, 81%, 68%, respectively; p < 0.001), survival (78%, 46%, 30%, respectively; p < 0.001), amputation-free survival (78%, 42%, 25%, respectively; p < 0.001), maintenance of ambulation (96%, 78%, 68%, respectively; p < 0.001), maintenance of independence (98%, 85%, 75%, respectively; p < 0.001), and resolution of presenting symptoms (79%, 61%, 42%, respectively; p < 0.001). CONCLUSIONS: There is a declining spectrum of outcomes performance from claudication to rest pain to tissue loss. These findings question the accuracy of all previously published data for critical limb ischemia, for which rest pain and tissue loss are usually blended and reported as a single outcomes value. PMID- 19476837 TI - Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, active target. AB - BACKGROUND: The recently discovered indoleamine 2,3-dioxygenase-2 (IDO2) gene has 2 functional polymorphisms that abolish its enzymatic activity. We hypothesize that expression of the IDO2 enzyme in primary pancreatic ductal adenocarcinomas (PDA) can help cancer cells evade immune detection. STUDY DESIGN: Because the IDO2 enzyme might be the preferential target of d-1-methyl-tryptophan, a clinical lead inhibitor of IDO currently being evaluated in phase I trials, we sequenced IDO2 in 36 pancreatic specimens and evaluated its expression. RESULTS: We found that 58% (21 of 36) of cases were heterozygous for the R248W polymorphism; 28% (10 of 36) were homozygous wild-type; and only 14% (5 of 36) were homozygous for the functionally inactive polymorphism. As for the Y359STOP polymorphism, we found that 27% (10 of 36) of cases were heterozygous, 62% (22 of 36) were homozygous wild-type, and only 11% (4 of 36) were homozygous for this functionally inactive allele. Ruling out the possibility of compound polymorphic variants, we estimated 75% of our resected patient cohort had an active IDO2 enzyme, with a conservative estimate that 58% of the patients had at least 1 functional allele. IDO2 was expressed in PDA tissue from each genetically polymorphic subgroup. We also detected IDO2 protein expression in the genetically distinct pancreatic cancer cell lines after exposure with interferon-gamma. CONCLUSIONS: This is the first study to report IDO2 expression in PDA and related cancers indicating that IDO2 genetic polymorphisms do not negate interferon-gamma inducible protein expression. Taken together, our data strongly suggest that the clinical lead compound d-1-methyl-tryptophan might be useful in treatment of PDA. PMID- 19476841 TI - Endovascular repair for diverse pathologies of the thoracic aorta: an initial decade of experience. AB - BACKGROUND: Endovascular grafts have rapidly evolved as a minimally invasive treatment for a variety of acute and chronic disorders of the thoracic aorta. Application of this technology at a single center is reported. STUDY DESIGN: Between 1998 and 2007, 197 patients underwent thoracic endovascular aortic repair. Primary indications included degenerative aneurysms (n = 121), type B aortic dissection (n = 44), mycotic aneurysms (n = 9), traumatic disruptions (n = 9), intramural hematoma (n = 5), pseudoaneurysm (n = 4), and miscellaneous pathology (n = 5). An analysis of patient demographics, periprocedural records, complications, reinterventions, and survival was conducted. RESULTS: Thirty-day mortality was 6%, which was lowest among patients undergoing treatment for a degenerative thoracic aortic aneurysm (2.4%, 3 of 121). Major adverse events included stroke in 3%, spinal cord ischemia in 2%, peripheral vascular repair in 4.5%, renal failure in 4.5%, and open conversion in one patient (0.5%). Both preoperative serum creatinine (odds ratio 1.44, 95% CI 1.02 to 2.04, p = 0.039) and number of endograft components (odds ratio 1.43, 95% CI 1.01 to 2.01, p = 0.043) were predictors of major adverse events. Kaplan-Meier analysis revealed a reduction in late survival among patients with preoperative creatinine >or=1.8 mg/dL (p < 0.001). One- and 5-year intervention-free survivals were 77%+/-3% and 41%+/-6%, respectively. CONCLUSIONS: Thoracic endovascular aortic repair represents an effective treatment for a variety of pathologic states. But the risk-benefit analysis for thoracic endovascular aortic repair should carefully consider the extent of disease, pathologic condition, and renal function. PMID- 19476839 TI - A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis. AB - BACKGROUND: Precepts about acute pancreatitis, necrotizing pancreatitis, and pancreatic fluid collections or pseudocyst rarely include the impact of pancreatic ductal injuries on their natural course and outcomes. We previously examined and established a system to categorize ductal changes. We sought a unifying concept that may predict course and direct therapies in these complex patients. STUDY DESIGN: We use our system categorizing ductal changes in pseudocyst of the pancreas and severe necrotizing pancreatitis (type I, normal duct; type II, duct stricture; type III, duct occlusion or "disconnected duct"; and type IV, chronic pancreatitis). From 1985 to 2006, a policy was implemented of routine imaging (cross-sectional, endoscopic retrograde cholangiopancreatography, or magnetic resonance cholangiopancreatography). Clinical outcomes were measured. RESULTS: Among 563 patients with pseudocyst, 142 resolved spontaneously (87% of type I, 5% of type II, and no type III, and 3% of type IV). Percutaneous drainage was successful in 83% of type I, 49% of type II, and no type III or type IV. Among 174 patients with severe acute pancreatitis percutaneous drainage was successful in 64% of type I, 38% of type II, and no type III. Operative debridement was required in 39% of type I and 83% and 85% of types II and III, respectively. Persistent fistula after debridement occurred in 27%, 54%, and 85% of types I, II, and III ducts, respectively. Late complications correlated with duct injury. CONCLUSIONS: Pancreatic ductal changes predict spontaneous resolution, success of nonoperative measures, and direct therapies in pseudocyst. Ductal changes also predict patients with necrotizing pancreatitis who are most likely to have immediate and delayed complications. PMID- 19476843 TI - Diagnosing ruptured appendicitis preoperatively in pediatric patients. AB - BACKGROUND: Over the past decade, pediatric patients with ruptured appendicitis (RA) have been successfully treated with IV antibiotics and an interval appendectomy. Because the treatment of acute appendicitis (AA) and RA in children is now diverging, distinguishing between these two conditions preoperatively is critical. STUDY DESIGN: A prospective cohort study was conducted. Clinical data were collected, and the attending surgeon's preoperative diagnosis was recorded. Accuracy of the pediatric surgeon's diagnosis was determined. Univariable and multivariable logistic regression were then used to determine independent clinical predictors of RA. Using the relative beta coefficients of these predictors, a scoring system was constructed to aid in the diagnosis of RA. RESULTS: Two hundred forty-seven patients were evaluated: 98 AA (40%), 53 RA (21%), and 97 not appendicitis (39%). Median age was 10 years old. The overall accuracy of the pediatric surgeon's preoperative diagnosis was 92%. Sensitivity and specificity for the diagnosis of RA were 96% and 83%, respectively. Multivariable regression analysis identified generalized tenderness on examination, duration of symptoms longer than 48 hours, WBC>19,400 cells/microL, abscess, and fecalith on CT scan as independent predictors for RA. A novel scoring system was developed with these variables, and, when applied to the study population, the specificity for the diagnosis of RA improved to 98%. CONCLUSIONS: Pediatric surgeons differentiate AA from RA and not appendicitis preoperatively with high accuracy and sensitivity, but the specificity for diagnosing ruptured appendicitis is lower. The scoring system improved the specificity of the preoperative diagnosis. The validity and utility of this scoring system should be examined in future studies in larger patient populations. PMID- 19476847 TI - Simultaneous versus staged resection for synchronous colorectal cancer liver metastases. AB - BACKGROUND: The aim of this study was to compare postoperative outcomes of patients with synchronous colorectal liver metastases treated with either simultaneous or staged colectomy and hepatectomy. STUDY DESIGN: From July 1997 to June 2008, a review of our 1,344-patient prospective hepato-pancreatico-biliary database identified 230 patients treated surgically for primary adenocarcinoma of the large bowel and synchronous hepatic metastasis. Clinicopathologic, operative, and perioperative data, complications, and grade of complications (grade 1, minor, to grade 5, death) were reviewed to evaluate selection criteria, operative methods, and perioperative outcomes. Chi-square and proportional hazard model were used to evaluate predictors of outcomes. RESULTS: Seventy patients underwent simultaneous resection of colon primary and liver metastasis in a single operation; 160 patients underwent staged operations. Simultaneous resections were similar for size (median 4 cm versus 3.7 cm) and number (median 3 cm versus 3 cm) of liver metastases. Major liver resections (>or=3 Couinaud segments) were similar between staged and simultaneous (32% versus 33%, respectively), as was type of colectomy (p=0.2). Complication rates and severity were similar in both groups: 39 of 70 patients (56%) in the simultaneous group experienced 63 complications versus 88 of 160 patients (55%) with 162 complications in the staged group (p=0.24). Multivariate analysis identified blood transfusion as a predictor of complication (odds ratio 2.98, p=0.001). Patients having simultaneous resection required fewer days in the hospital (median 10 days versus 18 days, p=0.001). CONCLUSIONS: By avoiding a second laparotomy, simultaneous colon and hepatic resection reduces overall hospital stay, with no difference in morbidity and mortality rates or in severity of complications, compared with staged resection. Simultaneous resection is an acceptable option in patients with resectable synchronous colorectal metastasis. PMID- 19476845 TI - Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: who really benefits? AB - BACKGROUND: The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN: Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS: There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n=374) and those receiving adjuvant CRT (n=299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p=0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p=0.034). CONCLUSIONS: This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID- 19476849 TI - African-American and low-socioeconomic status patients have a worse prognosis for invasive ductal and lobular breast carcinoma: do screening criteria need to change? AB - BACKGROUND: Determine the effect of race, socioeconomic status (SES) and other demographic variables on outcomes of patients with invasive ductal and lobular breast cancer. STUDY DESIGN: Florida cancer registry and inpatient hospital data were queried for patients diagnosed with invasive breast cancer from 1998 to 2002. RESULTS: A total of 63,472 patients with breast cancer were identified. Overall, 90.5% of patients were Caucasian, 7.6% African American, and 8.7% Hispanic. African-American patients presented at a younger age and with more advanced disease, 10.5% presented with breast cancer before the age of 40 years, and 22.4% before 45 years of age. African-American patients were less likely to undergo operations. Similarly, low-SES patients were less likely to have operations and presented more often with larger tumors. Stepwise multivariate analysis revealed a substantial drop in the hazard ratio for African-American patients once correction for stage of presentation was made, suggesting that disparities in breast cancer outcomes are, in part, a result of advanced stage at presentation. Race and low SES were independent predictors of worse prognosis when controlling for patient comorbidities and treatment. CONCLUSIONS: Dramatic disparities by patient race and SES exist in breast cancer. Our study integrates previous smaller studies, providing comprehensive insight into African-American patients and their outcomes for breast cancer. Earlier screening programs and greater access to cancer care for the poor and African Americans are needed. Successful institution of such programs will not completely erase disparities in outcomes for breast cancer in African-American patients. PMID- 19476851 TI - Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. AB - BACKGROUND: Multidetector computed tomography (MDCT) scanning technology has increased the ease with which pulmonary emboli (PE) are evaluated. Our aim was to determine whether the incidence and severity of postoperative PE have changed since adoption of multidetector computed tomography. STUDY DESIGN: A prospective postoperative morbidity and mortality database from a single institution was used to identify all cancer patients who experienced a PE within 30 days of thoracic, abdominal, or pelvic operations. The incidence, type (central, segmental, and subsegmental), and severity of PE were examined. RESULTS: A total of 295 PE were documented among 47,601 postoperative cancer patients. The incidence of PE increased yearly from 2.3 per 1,000 patients in 2000 to 9.3 per 1,000 patients in 2005 (p < 0.0001). This corresponded to an increasing number of CT scans of the chest performed (6.6 CT scans per 1,000 postoperative patients in 2000 versus 45 in 2005; p < 0.0001). The increased incidence was because of a 7.8% (CI, 4.0 to 11.7) and 5.4% (CI, 4.1 to 6.7) average annual increase in segmental and subsegmental PE, respectively. There was no change in the number of central (0.1%; CI, -1.0 to 1.12) PE. Overall incidence of fatal PE was 0.4 and did not change during the time period (p = 0.3). A central PE was more commonly associated with hypoxia, ICU admission, and 30-day mortality (33% versus 5% for peripheral; p = 0.02). CONCLUSIONS: Chest CT scans are being performed more frequently on postoperative cancer patients and have resulted in an increased diagnosis of peripheral PE. The clinical significance of, and optimal treatment for, diagnosed subsegmental PE are incompletely defined. PMID- 19476853 TI - Drain amylase levels are an adjunct in detection of gastrojejunostomy leaks after Roux-en-Y gastric bypass. AB - BACKGROUND: Because anastomotic leaks after gastric bypass surgery can have devastating consequences for the patient, early detection is highly desirable. This and many other bariatric surgical centers have discontinued routine use of upper gastrointestinal contrast x-ray because of the lack of cost-effectiveness, discomfort to the patient, and the failure of the study to detect some leaks. We postulated that drain amylase levels from a juxta-anastomotic drain would detect the presence of salivary amylase and be a sensitive test for gastrojejunostomy leak. STUDY DESIGN: Routine measurement of amylase levels from a drain adjacent to the gastrojejunostomy was instituted in 2005. Leak was defined as anastomotic incompetence documented either by confirmatory upper gastrointestinal contrast x rays, CT scans, or reoperation. RESULTS: On postoperative day 1, the drain amylase levels of 350 patients were tested. Seventeen patients had postoperative leaks (4.8%); 14 of the 17 had leaks at the gastrojejunal anastomosis (82%). The median peak value for patients without leak was 79.5 IU/L+/-1,436.2 SD; for patients with leak it was 6,307 IU/L+/-50,166 (p < 0.0001, Wilcoxon rank sum test). All patients but one with a leak had a drain amylase > 400 IU/L. A drain amylase value of 400 IU/L empirically defines gastrojejunostomy leaks with a sensitivity of 94.1% and a specificity of 90.0%. Negative predictive value of a drain amylase level < 400 IU/L in excluding leak was 99.6%. Positive predictive value of a drain amylase > 400 IU/L in predicting leak was 33.3%. Of the 17 leaks, 7 required reoperation at a median of 1 day (mean, 1.6+/-1.1 days). There was no perioperative mortality. CONCLUSIONS: Drain amylase levels are a simple, low-cost adjunct with high sensitivity and specificity that can help to identify patients who may have a leak after gastric bypass surgery. PMID- 19476855 TI - The fallen one: the inferior parathyroid gland that descends into the mediastinum. AB - BACKGROUND: Inferior parathyroid glands are located along the embryologic migration path of the thymus and can rest in the thyrothymic ligament or anterior mediastinum. Our nomenclature system designates these glands as "fallen" (type F) glands. This study reviews our experience with type F parathyroid glands to determine which can be retrieved successfully through a cervical incision. STUDY DESIGN: A retrospective review of patients who underwent parathyroidectomy between June 1998 and May 2008 was performed. Patient demographics, localization studies, and operative and pathologic reports were analyzed. Distance from the superior aspect of the clavicle to the target parathyroid gland was measured. RESULTS: Sixty (9.2%) patients had a type F parathyroid gland. Parathyroidectomy was performed through cervical incision in 54 (90%) patients and 6 (10%) required a thoracic approach. Preoperative imaging identified parathyroid glands located >or=6 cm below the superior aspect of the clavicle in eight patients. Of these, six (75%) required a thoracic approach and two (25%) were resected through a cervical incision with concomitant thymectomy. Parathyroidectomy was successfully performed through a cervical incision in all 52 (100%) patients in whom the target parathyroid gland was <6 cm below the superior aspect of the clavicle (Fisher's exact test, p < 0.001). CONCLUSIONS: A cervical approach allows successful retrieval of type F parathyroid glands located <6 cm below the superior aspect of the head of the clavicle in the anterior mediastinum. Parathyroidectomy for glands located >or=6 cm below the superior aspect of the clavicle can be attempted from the neck with concomitant thymectomy, but the majority will require a thoracic approach. PMID- 19476857 TI - Vascular complications of orthotopic liver transplantation: experience in more than 4,200 patients. AB - BACKGROUND: Thromboses of the hepatic artery (HAT) and portal vein (PVT) may complicate orthotopic liver transplantation (OLT) and result in graft loss and mortality. Revision and retransplantation are treatment options, but their longterm outcomes remain undefined. This study was undertaken to evaluate the incidence of major vascular complications after OLT, determine efficacy of therapies, and identify factors influencing longterm outcomes. STUDY DESIGN: All patients undergoing OLT from 1984 to 2007 were evaluated. Kaplan-Meier analysis was performed to define the effects of vascular complications on posttransplant survival. Anastomotic revision and arterial thrombolysis were compared with retransplantation as treatment for HAT. After 2002, porta hepatis dissection was initiated with early occlusion of common hepatic artery (CHA) inflow; its impact on HAT incidence was determined. RESULTS: From 1984 to 2007, 4,234 OLTs were performed. HAT occurred in 203 patients (5%) and PVT in 84 (2%). Graft survival was significantly reduced by HAT or PVT; patient survival was reduced only by PVT. Retransplantation for HAT improved patient survival over revision or thrombolysis in the first year but did not provide longterm survival advantage (56% versus 56% at 5 years; p=0.53). Patients with HAT had only 10% graft salvage with anastomotic revision or thrombolysis. HAT was significantly reduced with early CHA inflow occlusion (1.1% versus 3.7%; p=0.002). Factors increasing risk of HAT included pediatric recipients, liver cancer, and aberrant arterial anatomy requiring complex reconstruction. CONCLUSIONS: Both HAT and PVT significantly reduce graft survival after OLT; PVT more adversely affects patient survival. Revision and thrombolysis rarely salvage grafts after HAT; retransplantation provides superior short-term, but not longterm, survival. Avoidance of vascular complications in OLT is critical, especially with today's scarcity of donor livers. Early atraumatic CHA occlusion significantly reduces the incidence of HAT. PMID- 19476861 TI - Pharmacologic prophylaxis against venous thromboembolic complications is not mandatory for all laparoscopic Roux-en-Y gastric bypass procedures. AB - BACKGROUND: Venous thromboembolism (VTE) is a leading cause of postoperative mortality in bariatric surgical patients. The aim of this study is to report the rate of VTE and bleeding complications using no prophylactic pharmacologic anticoagulation among patients undergoing laparoscopic Roux-en-Y gastric bypass. STUDY DESIGN: Nine hundred fifty-seven consecutive patients who were older than 18 years, had no history of VTE, and had laparoscopic Roux-en-Y gastric bypass by a single surgeon (RHC) between January 2000 and October 2008 were included. Outcomes, including deep vein thrombosis and pulmonary embolism, were prospectively collected and retrospectively analyzed using SAS (version 9.1, SAS Institute Inc). VTE prophylactic regimen consisted of calf-length pneumatic compression devices placed before anesthesia induction and mandatory ambulation beginning on the day of operation. No prophylactic pharmacologic anticoagulation was used. All data presented as mean +/- SEM. RESULTS: Of the 957 patients, 792 were women and 165 were men. Mean age was 41.0 +/- 0.3 years, body mass index (calculated as kg/m(2)) was 49.1 +/- 0.2, and American Society of Anesthesiology scores 2 (29.8%), 3 (69.8%), and 4 (0.4%). Mean operative time was 106.0 +/- 0.8 minutes. Clinically evident deep vein thrombosis developed in three patients (0.31%) and one patient had a pulmonary embolism (0.10%). The one mortality in the cohort was unrelated to VTE. There were seven (0.73%) bleeding complications, of which one resolved without treatment, two required reoperation, and four required blood transfusions. CONCLUSIONS: Adequate VTE prophylaxis is achieved using calf-length pneumatic compression devices, early ambulation, and relatively short operative times. Pharmacologic anticoagulation is not mandatory when these conditions are met in patients who have no earlier history of VTE. There are few bleeding complications requiring reoperation or blood transfusions without the use of anticoagulants. PMID- 19476859 TI - Improved surgical outcomes for breast cancer patients receiving neoadjuvant aromatase inhibitor therapy: results from a multicenter phase II trial. AB - BACKGROUND: Neoadjuvant aromatase inhibitor therapy has been reported to improve surgical outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer. A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice. STUDY DESIGN: One hundred fifteen postmenopausal women with >2 cm, estrogen receptor (ER) or progesterone receptor (PgR)-positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.5 mg daily before operation. RESULTS: One hundred six patients were eligible for primary analysis, 96 underwent operations, 7 received chemotherapy after progressive disease, and 3 did not undergo an operation. Baseline surgical status was marginal for breast-conserving surgery (BCS) in 48 (45%), 47 were definitely ineligible for BCS (44%), and 11 were inoperable by standard mastectomy (10%). Overall Response Evaluation Criteria In Solid Tumors clinical response rate in the breast was 62%, with 12% experiencing progressive disease. Fifty percent underwent BCS, including 30 of 46 (65%) patients who were initially marginal for BCS and 15 of 39 (38%) patients who were initially ineligible for BCS. All 11 inoperable patients successfully underwent operations, including 3 (27%) who had BCS. Nineteen percent of patients undergoing mastectomy had a pathologic T1 tumor, suggesting that some highly responsive tumors were overtreated surgically. CONCLUSIONS: Neoadjuvant aromatase inhibitor improves operability and facilitates BCS, but there was considerable variability in responsiveness. Better techniques to predict response, determine residual tumor burden before operation, and greater willingness to attempt BCS in responsive patients could additionally improve the rate of successful BCS. PMID- 19476863 TI - Metastatic melanoma cells in the sentinel node cannot be ignored. AB - BACKGROUND: How to best risk-stratify patients with metastatic melanoma in the sentinel node (SN) is controversial. Not all node-positive disease is equivalent in terms of disease-free or overall survival, and some have suggested that submicrometastatic disease, characterized by <0.1 mm tumor burden, can represent a distinct classification not associated with a chance for recurrence or death. We hypothesize that all patients with metastatic melanoma cells in the sentinel node have potentially life-threatening disease. STUDY DESIGN: This is a retrospective review of an IRB-approved, prospectively maintained melanoma database of >1,100 patients. All invasive melanoma patients who had an SN biopsy and at least 1 year of followup were included. Patients with metastatic melanoma in the SN were divided into groups according to diameter of SN tumor burden: node negative, <0.1 mm (submicrometastatic), 0.1 to 1.0 mm, and >1.0 mm. Statistical methods included the Jonckheere-Terpstra method, Fisher's exact tests, and Kaplan Meier method. RESULTS: From July 1, 1998 to July 1, 2007, 578 patients with invasive melanoma underwent SN procedure. Median followup was 2.2 years. There was a statistically significant difference in the proportion of patients who experienced a recurrence between the node-negative group (11%) and the <0.1 mm group (24%) (p = 0.049). Patients in the submicrometastatic group have a statistically significant (p = 0.048) earlier recurrence than those in the node negative group. CONCLUSIONS: These results suggest that patients with submicrometastatic SN disease should not be treated as node-negative, as it appears to represent a more biologically aggressive melanoma, associated with a substantially faster time to recurrence. We cannot agree with recent proposals that patients with very small tumor burden in the SN can be treated as node negative and be spared completion node dissection. PMID- 19476865 TI - Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients. AB - BACKGROUND: Transfusion of packed red blood cells (PRBCs) increases morbidity and mortality in select surgical specialty patients. The impact of low-volume, leukoreduced RBC transfusion on general surgery patients is less well understood. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program participant use file was queried for general surgery patients recorded in 2005 to 2006 (n = 125,223). Thirty-day morbidity (21 uniformly defined complications) and mortality, demographic, preoperative, and intraoperative risk variables were obtained. Infectious complications and composite morbidity and mortality were stratified across intraoperative PRBCs units received. Multivariable logistic regression was used to assess influence of transfusion on outcomes, while adjusting for transfusion propensity, procedure type, wound class, operative duration, and 30+ patient risk factors. RESULTS: After adjustment for transfusion propensity, procedure group, wound class, operative duration, and all other important risk variables, 1 U PRBCs significantly (p < 0.05) increased risk of 30-day mortality (odds ratio [OR] = 1.32), composite morbidity (OR = 1.23), pneumonia (OR = 1.24), and sepsis/shock (OR = 1.29). Transfusion of 2 U additionally increased risk for these outcomes (OR = 1.38, 1.40, 1.25, 1.53, respectively; p